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CELL ENVIRONMENT & CELL JUNCTIONS
DEPARTMENT OF PERIODONTOLOGY
AND ORAL IMPLANTOLOGY
GUIDED BY- DR.VINITI GOEL
PRESENTED BY- DR.MANISHA
DEOL
MDS 1YEAR
CONTENTS
 INTRODUCTION
 HOW CELL TURNS NUTERIENTS INTO USABLE
ENERGY ?
 WHAT SPECIFIC PATHWAYS DO CELLS USE ?
 BODY FLUIDS
 DERANGEMENTS OF BODY FLUID
 HOMEOSTASIS
 DISTURBANCES OF ELECTROLYTE
 INTERACTION OF EXTRACELLULAR
ENVIRONMENT WITH ITERCELLULAR
ENVIRONMENT
 CELL JUNCTIONS
 CONCLUSION
 REFRENCES
INTRODUCTION
 PLASMA MEMBRANE
constitutes the boundary
between a living cell and its non-
living environment , materials
present outside the plasma
membrane play an important role
in the life of a cell.
 The ability of tissue cell to stick to
one another is critical for many
physiological and pathological
processes.
HOW CELL TURNS NUTRIENTS INTO USABLE ENERGY?
CELL do not use the energy from oxidative
reactions as soon as it is released. They
convert it into small, energy -rich molecules
such as ATP &NADH(nicotinamide adenine
dinucleotide).Enzymes(workhorse
proteins)used this chemical energy to
catalayze , or accelerate the reactions .
Enzyme allow the activation energies to be lowered.
WHAT SPECIFIC PATHWAYS DO CELLS USE?
 IN EUKARYOTIC CELLS, THREE MAJOR PATHWAYS ARE USED
TO TRANSFER ENERGY INTO MORE READILY USABLE FORM-
ATP
 ATP, is the most abundant energy carrier molecule in the cells.
FIRST PROCESS IN THE EUKARYOTIC ENERGY PATHWAY
 GLYCOLYSIS means Sugar splitting.
 It occurs in cytoplasm.
 In this ,single molecule of glucose (6-c) is splitting into two
molecules of pyruvate (3-c).
 Glycolysis is actually a series of 10 chemical reactions that
require the input of 2 ATP MOLECULES.
 This input is used to generate 4 new ATP MOLECULES and
NADH IS also produced.
 In aerobic condition by glycolysis , cell produce pyruvate(32
ATP) or in anaerobic condition lactate (2 ATP).
 Fermentation(DOES NOT REQIURE ENERGY) is also a ancient ,
major producing pathway that occurs in almost all cells .
SECOND PROCESS IN THE EUKARYOTIC ENERGY
PATHWAY
 CITRIC ACID CYCLE or KREBS CYCLE or TRICARBOXYLIC ACID
CYCLE(TCA cycle).
 When the oxygen is available , the pyruvates produced by glycolysis
become the input for the next portion of the eukaryotic energy pathway.
 During this stage ,each pyruvate molecule in the cytoplasm enters the
mitochondrion , where it is converted in to ACETYL CO-A.
 ACETYL CO-A is a two –carbon energy carrier ,and the third –carbon
combines with oxygen and it is released as carbon dioxide.
 At the same time , an NADH carrier is generated.
 Acetyl CO-A then enters a pathway called CITRIC ACID CYCLE.
 IT is a 8 step chemical reaction, generates 3 more NADH molecules and 2
other carriers (FADH2 and GTP).
 2-C ACETYL CO –A + 2-COXALOACETATE =6-C TRICARBOXYLIC ACID.
 Total 24 ATP molecules are produced by this cycle.
THIRD PROCESS IN THE EUKARYOTIC ENERGY
PATHWAY
 ELECTRON TRANSPORT CHAIN , catalyzed by several protein complexes
located in the mitochondrional inner membrane. This process called
OXIDATIVE PHOSPHORYLATION.
 IT TRANSFERS ELECTRON from NADH AND FADH2. through the
membrane protein complexes , ultimately to oxygen ,where they
combines to form water.
 As the electron , travel through the protein complexes in the chain , a
gradient of hydrogen ions , or protons , forms across the mitochondrial
membrane.
 CELL used the energy of this proton gradient to create 3 additional ATP
molecules for every electron that travels along the chain.
 Together this processes occur in the mitochondria called
RESPIRATION , a term used for processes that couple the uptake of
oxygen and production of Carbon dioxide.
BODY FLUIDS
 Body is made up of solids and fluids. Fluid part is more than two third
of the whole body. Water forms most of the fluid part of the body.
 Total water in body is about 40L
It is distributed into two major components:-
 Intracellular fluid (ICF) :-22L in volume and is 55% of total body water.
 Extracellular fluid (ECF) :-18L in volume and is 45%of total body
water.
ECF is divided into
ECF is divided into 5
subunits:
 Interstitial fluid and lymph (20%)
 Intravascular fluid / Plasma
(7.5%)
 Mesenchymal fluid / Fluid in
dense connective tissues like
cartilage (7.5%)
 Fluid in bones (7.5%)
 Transcellular fluid (2.5%) that
includes:
a) Cerebrospinal fluid
b) Intraocular fluid
c) Digestive juices
d) Synovial fluids in joints
e) Fluid in urinary tract
d) Serous fluid- intrapleural
fluid,
pericardial fluid and peritoneal
fluid.
 ECF contains large
quantity of sodium, chloride,
bicarbonate, glucose,
fatty acids and oxygen
 ICF contains large quantity
Potassium, Phosphate ,
magnesium,
Small amount of sodium,chloride,
 pH of ECF = 7.4 and
pH ICF = 7.0
Dehydration
 State of deprivation of water. Corresponding loss of
electrolytes’
 Pathogenesis : decrease of body water decrease blood
volume withdrawal of fluid from interstitial
compartment with hyperosmolality . shifting of
intercellular water to extracellular compartment resulting in
cellular dehydration.
 Causes
Deficient water intake. e.g. dysphagia, starvation.
Excessive loss of water. e.g. diabeties insipidus,
pyrexia
Applied physiology
Dehydration
 Dehydration is defined as the excessive loss of water from the body.
 Daily water requirement is 1litre and for active individual 2-3 liters
 Mild dehydration: fluid loss is about 5%of total body fluids
 Moderate dehydration: fluid loss is about 10% of total body fluids
 Severe dehydration: fluid loss is more than 15% of total body fluids.
 Causes are:- severe diarrhea and vomiting, excess urinary output ,
insufficient intake of water, excess sweating, use of laxatives or
diuretics.
Water intoxication or Overhydration
 Condition characterized by great increase in water content
of the body.
 Also known as hyperhydration , water excess or water
poisoning.
 When kidney have a restricted ability to dilute the urine.
 when large amounts of pure water is given. It results in
expansion of extracellular fluid compartment or sodium in
your blood to drop too low (hyponatreima) with reduced
osmolality and intracellular edema.
Derangements in body fluids
Causes :
 a)Heart failure in which heart cannot pump blood properly.
 b) Renal disorders.
 c) Hypersecretion of anti diuretic hormone (vasopressin).
 d) IV or oral administration of unduly large amount of medication
and fluids. eg drugs containing estrogen , hormone
replacement therepy , NSAID’S
 e) Infants is first month of life as kidney is underdeveloped.
 f) An adult whose liver and heart working normally can develop
overhydration rarely if person consumes 8L water everyday
regularly
 g) Children having swimming practice.
Edema
 Abnormal or excessive collection of fluid in the interstitial tissue
space and serous cavities.
 Edema may be of different types:
1. Localized- Inflammatory , lymphatics , toxic ,
2. allergy.
3. Generalized- renal , cardiac , nutritional.
4. Special- Pulmonary , cerebral.
 Edema fluid can be : Transudate or Exudate.
DISTUBANCES IN ELECTROLYTES
 The pH of arterial plasma is normally 7.40 +0.5 or -0.5 and venous
plasma is slightly lower.
 Decrease in pH below normal is acidosis.
 Increase in pH above normal is alkalosis.
 It depends on :
1.concentration of bicarbonate ion.
2.pCO2 that determines concentration of bicarbonate.
METABOLIC ACIDOSIS:
 Fall in pH because of fall of bicarbonate ions and increased
H+ ions . E.g. lactic acidosis , chronic renal failure.
 This occurs when strong acids are added to blood. E.g. If
large amount of acid is ingested. E.g. , in Aspirin overdose
acids in blood are quickly increased lowering the available
buffers.
METABOLIC ALKALOSIS:
Rise in pH due to rise in HCO3-
level of plasma and loss of H+
ions .
E.g. Severe and prolonged vomiting, Cushing’s syndrome .
RESPIRATORY ACIDOSIS:
 Fall in blood pH due to raised Pco2 as a consequence to under
ventilation of lungs. E.g. Air obstruction in bronchitis, asthma.
Rise in blood pH due to lowered Pco2 as a
consequence to hyperventilation of lungs. E.g.
Hysterical over breathing, working at high
temperature, at high altitudes.
RESPIRATORY ALKALOSIS
Homeostasis
 Homeo = same ; Stasis = standing.
 ‘Homeostasis’ refers to maintenance of constant internal environment of
the body.
 In 19th century great biologist Claude Bernard said that multicellular organism
including man live in a perfectly organized and controlled internal
environment, which he called as ‘milieu interieur’.
 The term homeostasis was coined by Harvard Professor,
Walter B Cannon in 1930.
Role of various system of the body in
homeostasis
 The ph of the ECF has to be maintained at the critical value of 7.4.
Tissue cannot survive if this is altered. Decrease in ph is known as
acidosis, or increase in ph is known as alkalosis. Respiratory system, blood
and kidney help in regulation of ph.
 Ideal body temperature is 37.5 degree Celsius. Alteration in this temperature
alters metabolic activity of cell.
 Skin, respiratory system, digestive system, excretory system, skeletal
muscle and nervous system maintains the body temperature.
 Nutrients are essential for variety of cells and
growth of tissue. Nutrients must be digested,
absorbed into blood and supplied to cells.
Digestive and circulatory system play a major role
in supply.
 Adequate amount of oxygen should be supplied to
cell as well as carbon dioxide and other waste
products should also be removed. Respiratory
system is involved in supply of oxygen and removal
of carbon dioxide while kidneys and excretory
 Hormones are essential for the metabolism of
nutrients and other substance necessary for the
cell. Endocrine system help to maintain the
synthesis and release of appropriate amount of
hormones.
 Water and electrolyte balance should be
maintained. Otherwise it will lead to dehydration,
water toxicity and alteration in osmolality of body
fluids. Kidney, skin ,salivary glands and GIT takes
care of this.
NORMAL WATER BALANCE
 Average water intake is 2800 ml / day.
 Water is eliminated from the body via kidney in the form of urine (1500
ml/day), via skin (800ml/ day), via lungs (400ml/day), via faces
(100ml/day).
NORMAL ELECTROLYTE BALANCE
 A number of acids such as carbonic, phosphoric,
sulfuric, lactic, hydrochloride, ketoacids are formed
during normal metabolic activity.
 Regulation of Acid Base Balance occurs with the
help of a Buffer System.
 Buffers are weak acids and strong bases which limit
change in H+ ion concentration by taking up H+
when pH rises.
 They form first line of defense in regulating pH.
Interaction between extracellular and intracellular
environment:
 Cell membrane allows water & nonpolar molecules
to permeate by simple diffusion cell membranes ,
however also have to allow passage of various polar
molecule such as ions, sugars, amino acids,
nucleotides and many cell metabolites.
 Membrane proteins are responsible for this
transferring of solute across cell membrane known
as membrane transport proteins.
 There are two major classes of proteins.
-Carrier proteins
-Channel proteins
 The lipid bilayer cell membrane of cell is not
miscible with either the extracellular fluid or the
intracellular fluid.
 Therefore, it constitutes a barrier against movement
of water molecules and water-soluble substances
between the extracellular and intracellular fluid
compartments.
Exchange mechanisms
Cell membrane transport: exchange mechanism
 PASSIVE PROCESSES
-Simple Diffusion
-Facilitated Diffusion: Osmosis (require carrier protein)
 ACTIVE PROCESSES
-Active transport (require carrier protein and energy)
-Vesicular or bulk transport
1. Exocytosis
2.Endocytosis ( Phagocytosis &
Pinocytosis)
Passive transport:
 Transport along the concentration gradient or electrical gradient or
both electrochemical gradient is called passive transport it is also
known as diffusion or downhill transport.
 It does not need energy.
 It is of two types:
- Simple Diffusion
-Facilitated Diffusion
SIMPLE DIFFUSION
 Kinetic movement of molecules or ions occurs through
intermolecular spaces without any interaction with carrier
proteins in the membrane.
 Diffusion rate is related to temperature, pressure, state of
matter, concentration gradient, and surface area of membrane.
 Rate of diffusion is determined by amount of substances
available, the velocity of kinetic motion, number and sizes of
opening in cell membrane through which molecule or ions can
move.
Simple diffusion can occur through cell membrane by two pathways:
1. Through interstices of lipid bilayer if the diffusing substance is lipid
soluble.
2. Through watery channels that penetrate all the way through some of
the large transport protein.
FACILITATED DIFFUSION
 Facilitated diffusion is the net movement of molecules from a high
concentration to a low concentration with the aid of channel or carrier
proteins.
 Carrier proteins aids passage of the molecules or ions through the
membrane by binding chemically with them and shuttling through the
membrane.
 E.g. Ions (Na+, K+, Cl-), Sugars (Glucose), Amino Acids, Small water
soluble molecules, and water
OSMOSIS
 Osmosis is the net diffusion of water across a selectively permeable
membrane from a region of high water concentration to one that has a
lower water concentration.
(Guyton A.C, Hall J.E-
The Book of Medical
Physiology. 11th edition)
TONICITY
 Tonicity refers to the total solute concentration of the solution outside
the cell. There are three types of tonicity:
1. ISOTONIC: no net movement of water.
2. HYPOTONIC: cell gain water and swell.
3. HYPERTONIC: cell loose water and shrink.
Active transport:
 Movement of substances against the chemical or electrical or both
(electrochemical) gradient is called active transport.
 Also kas uphill transport.
 It requires energy which is obtained by the breakdown of high
energy compounds ATP.
 Active transport is divided into two types according to the source
of the energy used for transport:
1. Primary active transport: Energy is derived directly from
breakdown of adenosine triphosphate (ATP) or of some other
high-energy phosphate compound.
2. Secondary active transport: Energy is derived secondarily from
energy that has been stored in the form of ionic concentration
differences between the two sides of a cell membrane, created
originally by primary active transport.
 In both instances, transport depends on carrier proteins that
penetrate through the cell membrane, as is true for facilitated
diffusion.
 However, in active transport, the carrier protein functions
differently from the carrier in facilitated diffusion because it is
capable of imparting energy to the transported substance to
move it against the electrochemical gradient.
Vesicular or bulk transport
 Large particles and other substances can be moved between
the external environment, the plasma membrane, and the
interior of the cell via:
a) Exocytosis
b)Endocytosis
-Phagocytosis
-Pinocytosis
Exocytosis
 It is the process by which a
vesicle moves from the
cytoplasm to the plasma
membrane where it discharges
its contents to the extracellular
space. There are two general
pathways of exocytosis:
1. Constitutive pathway
2. Regulated secretory pathway
 Constitutive pathway: continuous process where proteins are
secreted immediately after their synthesis, as seen in the
secretion of immunoglobulins by plasma cells and of
tropocollagen by fibroblasts.
 Regulated secretory pathway: proteins are concentrated and
transiently stored before they are excreted out of the cell, as
seen in the release of zymogens granules by chief cells of the
gastric mucosa and by acinar cells of the pancreas.
Endocytosis:
 Movement of large molecules
into the cell by engulfing them in
vesicles, using ATP energy is
known as endocytosis.
 It can be of two types:
1. Phagocytosis
2. Pinocytosis
PINOCYTOSIS PHAGOCYTOSIS
1.It is the bulk intake of fluid material by a
cell.
1. It is the intake of solid material from
outside to inside of cell.
2.Vesicles are small 100-200 nm in diameter. 2. Vesicles formed are large, 1-2μm in
diameter.
3.Membrane possesses receptor pits for
receiving the materials.
3. Receptor pits are absent.
4.Digestion or breakdown of absorbed food
may or may not occur. Accordingly a food
vacuole may or may not formed.
4. A digestive or food vacuole is formed
from a phagosome.
5.Lysosomes play no role in utilization of
absorbed materials if digestion is not
involved.
5. Lysosomes are essential because solid
substance taken in by phagocytosis
require digestion.
6. There is no exocytosis 6. The undigested parts of the solid
materials are thrown out by exocytosis .
(Guyton A.C, Hall J.E- The Book of Medical Physiology. 11th edition)
CELL JUNCTIONS
 When cell come into contact with one another, sometimes
with the extracellular matrix specialized junctions may form
at specific sites on contacting cell membrane.
 Cell junction is also known as intercellular bridge.
 These are abundant in epithelial tissues.
SPECIALIZED JUNCTION MAY BE
CLASSIFIED INTO SEVERAL DIFFERENT
CATEGORIES:
 OCCLUDING (TIGHT) JUNCTIONS/ZONULA
OCCLUDENS
 ADHESIVE JUNCTIONS
1. Cell-to-cell
Zonula adherens
Macula adherens
(Desmosomes)
2. CELL-TO-MATRIX
Focal adhesions
Hemidesmosomes
 COMMUNICATING (GAP) JUNCTIONS
Occluding junctions/ Tight junctions/ Zonula
Occludens
● Opposing cell membrane are held in close contact by the
presence of transmembrane adhesive proteins arranged in
anastomosing strands that encircle the cell.
● Intercellular space is obliterated at the tight junctions.
● Transmembrane adhesive proteins are:
-Occludin
-Members of Claudine
family
-
 Several cytoplasmic proteins associated with intercellular portion of
transmembrane proteins like:
-cell polarity related proteins
-vesicular transport related proteins
-kinases
-transcription factors
-tumour suppressor protein
 Some cytoplasmic protein of tight junction bind to actin filaments.
 BARRIER FUNCTION: Tight junctions controls the passage of
materials through the intercellular spaces (from interstitium to
the lumen of the gland).
 MAINTAINENCE OF CELL POLARITY: Fencing function maintain two major
domains of the cell membrane by keeping proteins in apical
region.
-Apical surface
-Basolateral surface
 FENCING FUNCTION: Tight junction prevents lateral movement of proteins
and lipids in cell membranes thus, act as a fence . Due to this it is
sometimes referred as impermeable junction.
 Tightness of junction is specifically related to claudin and is
correlated with number of strands of transmembrane proteins.
 BLOOD BRAIN BARRIER: These are present in brain capillaries and forms
the blood brain barrier, which prevent the entry of many substances
into brain and allows only lipid soluble substances like drugs and
steroid hormone to enter into brain.
● Tightness of junction is specifically related to claudin and
is correlated with number of strands of transmembrane
proteins.
● Tight junction joining salivary glands secretory cells have
only 2 or 3 Junctional strands and are relatively permeable
to water , whereas those joining salivary gland striated duct
cells may have 6 to 9 strands and are relatively
impermeable to water. The permeability of tight junctions in
some tissue may be regulated by certain neurotransmitter
and hormones.
Current model of tight junctions:
MOLECULAR BIOLOGY OF CELL
3rd edition
ALBERT BRAY LEWIS RAFF ROBERTS WATSON
● It is postulated that the
sealing
strands that hold
adjacent plasma
membranes together are
formed by
Continuous strands of
transmembrane
Junctional proteins,
which make
contact across the
intercellular
space and create a seal.
Leaky tight junctions:
In some situations occlusion of the gaps between the adjoining cells may be
incomplete and the junction may allow slow diffusion of molecules across it.
These are referred to as leaky tight junctions.
Applied physiology: disease caused if protein encoding
for tight junctions are mutated.
 Hereditary deafness
 Ichthyosis (genetic disorder –dry, scaly, thickened skin)
 Sclerosing cholengitis (inflammation of bile duct causing obstruction)
 Hereditary hypomagnesemia
 Synovial sarcoma (soft tissue cancer)
ADHESIVE JUNCTIONS
● These junctions hold the cells
together or anchor cells to
extracellular matrix.
● Intercellular space is maintained
at ~ 25nm-30 nm
● Important in cellular signalling.
● Their cytoplasmic components may interact with the
cytoskeleton, triggering changes in cell shape or motility or
with certain tumor suppressor molecule or may act as
nuclear transcription factors or co activators.
● Sometimes loss of cell-cell or cell-matrix contact may lead
to apoptosis . Whereas in other cases loss of contact may
lead to loss of polarity & differentiation or unregulated cell
proliferation.
They are of 2 types of adhering junctions:
 a. Cell to cell:
-Zonula Adherens
-Macula Adherens (Desmosomes)
 b. Cell to matrix: Hemi-Desmosomes
Zonula adherens
 Cell–to–cell adherens junction in epithelial sheets often forms a
continuous adhesion belts k/as zonula adherens around each of the interacting cells
in the sheets located near the apex just below the tight junctions.
 The adhesion belt in adjacent epithelial cells are directly opposed and
the interacting plasma membrane are held together by membrane linker
protein that are members of calcium dependent cell-cell adhesion
molecule called cadherins.
 Cytoplasmic adapters of cadherins : E cadherins, alpha and beta catenins
 Cytoskeletal components: Actin filaments
 Other: Nectin – it establishes initial adhesion site for e-cadherins
and other protiens.
 Sites: Adherens junctions are present in the intercalated disks in
heart between the branches of cardiac muscles. During the
contraction and relaxation of heart, cardiac muscle fiber are held
together by means of this junction. Adherens junction in skin
helps to withstand mechanical stress.
Diagram showing molecular structure of adhering
junction.
 Cadherins are
Membrane linker proteins.
 Cytoplasmic adapters are Catenins
alpha and beta. They interact with
Cytoplasmic domain of cadherin.
 Cytoskeletal component are
Actin filaments.
 Nectin is initial adhesion site
E-cadherins & other proteins.
 P120 catenin stabilize the junction.
Affadin links nectin to actin filament.
Alpha actinin & ponsin links affadin and
Vinculin.
Ten Cate’s
Macula adherens /desmosomes
 Desmosomes is a cell-cell junction , where intermediate
filament connect two adjacent cells to form continuous network
through out the tissue.
 Also called macula adherens.
 These are button like points of intercellular contact that rivets
cell together.
 Intermediate filaments are attached with thickened patches.
 Some of these filaments are parallel to membrane others are
arranged in radiating fashion.
 The transmembrane protein present mainly belong to cadherin
family of calcium dependent cell-cell adhesion molecule.
 The cadherins are desmoglein and desmocollin. The interaction of
these transmembrane protiens with those of the adjacent cells
results in dense line in middle of intercellular space at the
desmosome.
 Catenins are desmoplakin, plakoglobin, plakophilin. These form
electrodense plaque on cytoplasmic side of desmosome. These
plaque serve as attachment site for cytoskeletal component which
are intermidiate filaments.
Desmosome in gingival epithelium
 Cohesion between merkel cells and between stratum spinosum of
keratinized gingival epithelium is provided by desmosomes.
 A desmosome may be considered to be 2 hemidesmosomes facing one
another, separated by a zone containing electron dense granulated
material (GM).
Thus a desmosome comprises the following
structural components:
1. The outer leaflets (OL) of the cell membrane of two
adjoining cells.
2. The thick inner leaflets (IL) of the cell membranes.
3. The attachment plaques (AP) which represent granular
and fibrillar material in the cytoplasm.
The presence of a large number of desmosomes indicates
that the epithelial cells are solid.
Clinical Periodontology and Implant Dentistry by Jan Lindhe , 5th edititon
 This is the diagram from the stratum
basale to the stratum granulosum.
 Both the no of tonofilaments (f) in the
cytoplasm & no of desmosomes (D)
increases.
 No of organelles such as mitochondria
(M), lamellae of RER (E) , golgi
complexes (G) decreases in
keratinocytes on their way from basal cell
layer to surface.
 In stratum granulosum, electron dense
keratohyline bodies & clusters of
glycogen containing granule start to occur
Applied physiology:
 The importance of desmosomes in holding cells together is
demonstrated by form of potentially fatal disease, pemphigus. In
which individual make antibodies against one of their own
desmosomal cadherin protiens these antibodies binds to and
disrupts desmosomes between skin epithelial cells causing
severe blistering as a result of leakage of body fluids into
loosened epithelium.
Hemidesmosomes (cell-matrix junction)
 They are the variant of the spot like adhering junctions, has
the structure of only half a desmosome.
 This type of junction bonds epithelial cells to their underlying
basement membrane and is well developed under the basal
layer of the epidermis.
 Protiens involved are mainly integrins.
Interface between basal cells of gingival
epithelium and basal lamina or basement
membrane facing connective tissue
BC: basal cell
LL: lamina lucida
LD: lamina densa
HD: hemidesmosome
AF: anchoring fibres
CT: cytoplasmic
tonofilaments
(Clinical Periodontology and Implant Dentistry by Jan Lindhe , 5th edititon)
Interface between junctional epithelium and tooth
 E: enamel
 1: space between JE & E,
continuation LD in the
basement membrane of
the connective tissue side.
 2: continuation of LL
LL: lamina lucida
LD: lamina densa
AF: anchoring fibres
(Clinical Periodontology and Implant Dentistry by Jan Lindhe , 5th edititon)
Epithelial rests are surrounded by a distinct basal lamina,
and are interconnected by hemidesmosomes and contain
tonofilaments
(Clinical Periodontology and Implant Dentistry by Jan Lindhe , 5th edititon)
Applied physiology:
 Like desmosomes some , the adapter proteins , bullous
pemphigoid antigen 230 (BP230) & plectin , form a dens plaque on the
cytoplasmic surface of hemidesmosomes which functions as
the attachment site for intermediate filaments.
Communicating /Gap junction
 Gap junctions are plaque like regions of cell membrane where
intercellular space narrows to 2 nm to 3 nm & transmembrane protiens
of connexin family forms aqueous channels between the cytoplasm of
adjacent cells.
 Permeability properties of a gap junction depends on the distribution of
specific proteins in specific tissues.
(Ten cate’s)
 6 connexin molecule forms a connexon which has a central channel of
2 nm in diameter.
 Connexon in one cell gets paired with the connexon of adjacent cell to
create a patent channel.
 Small molecule like ions and signalling molecules can move readily
from one cell to another & allows coordinated response to the stimulus
by the cells that are interconnected.
 These channels in the gap junction enable ions and small
molecules including amino acids, sugars, nucleotides, and
steroids to pass directly from one cell to another without the
need for such constituents to enter the intercellular space.
 Gap junctions are important where rapid communication
between adjacent cells is required as in smooth and cardiac
muscles.
 In smooth muscles: gap junction is called a nexus.
Ten cate’s
 In cardiac muscles: gap junction forms a part of intercalated
disc.
 Diameter of the channel is controlled by the calcium level , if
clalcium level increases the diameter decreases and if calcium
level decreases diameter increases.
 Diameter also depends upon pH , electrical potential , hormones
and neurotransmitters.
Gap junction diagram &electron micrographs
 Single connexon consists of 6
connexin molecule.
 Central channel Is
aopproximately 2nm in diameter.
Applied physiology:
Mutations in genes coding for connexins may cause:
 Deafness
 Keratoderma (thickening of skin on palms and soles)
 Cataract
 Peripheral neuropathy
 Heterotaxia (abnormal arrangements of right and left symmetry of body
organs or parts).
Conclusion:
 Cells in tissues are linked to one another and to the
extracellular matrix at specialized contact sites called cell
junctions. Thus , becoming chemically and electrically
coupled.
 As long as normal conditions are maintained in the internal
environment , cell of the body continuous to live and function
properly.
 Each cell contributes in homeostasis & each cell benefits from
homeostasis in turn . This reciprocal interplay provides
continuous automaticity to the body . If it is disturbed then all
cells suffer.
References
 Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson J.D- Molecular
Biology of The Cell, 3rd edition.
 Guyton A.C, Hall J.E- The Book of Medical Physiology, 11th edition.
 Kim E.Barrett, Susan M.Barmun, Scott Boitano, Hedwnn L.Brook’s
GANONG’S REVIEW OF MEDICAL PHYSIOLOGY, 23rd edition
 K.SEMBULINGAM Essential Of Medical Physiology
 Molecular and Cell biology of the Gingiva, PERIODONTOLOGY 2000,
VOL 24, PG 28-55
 Essentials of cell biology ,book by alexander johnson , dennis bray,
julian lewis and peter walter
1.cell environment & junctions Dr. Manisha

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1.cell environment & junctions Dr. Manisha

  • 1.
  • 2. CELL ENVIRONMENT & CELL JUNCTIONS DEPARTMENT OF PERIODONTOLOGY AND ORAL IMPLANTOLOGY GUIDED BY- DR.VINITI GOEL PRESENTED BY- DR.MANISHA DEOL MDS 1YEAR
  • 3. CONTENTS  INTRODUCTION  HOW CELL TURNS NUTERIENTS INTO USABLE ENERGY ?  WHAT SPECIFIC PATHWAYS DO CELLS USE ?  BODY FLUIDS  DERANGEMENTS OF BODY FLUID  HOMEOSTASIS  DISTURBANCES OF ELECTROLYTE  INTERACTION OF EXTRACELLULAR ENVIRONMENT WITH ITERCELLULAR ENVIRONMENT  CELL JUNCTIONS  CONCLUSION  REFRENCES
  • 4. INTRODUCTION  PLASMA MEMBRANE constitutes the boundary between a living cell and its non- living environment , materials present outside the plasma membrane play an important role in the life of a cell.  The ability of tissue cell to stick to one another is critical for many physiological and pathological processes.
  • 5. HOW CELL TURNS NUTRIENTS INTO USABLE ENERGY? CELL do not use the energy from oxidative reactions as soon as it is released. They convert it into small, energy -rich molecules such as ATP &NADH(nicotinamide adenine dinucleotide).Enzymes(workhorse proteins)used this chemical energy to catalayze , or accelerate the reactions .
  • 6. Enzyme allow the activation energies to be lowered.
  • 7. WHAT SPECIFIC PATHWAYS DO CELLS USE?  IN EUKARYOTIC CELLS, THREE MAJOR PATHWAYS ARE USED TO TRANSFER ENERGY INTO MORE READILY USABLE FORM- ATP  ATP, is the most abundant energy carrier molecule in the cells.
  • 8. FIRST PROCESS IN THE EUKARYOTIC ENERGY PATHWAY  GLYCOLYSIS means Sugar splitting.  It occurs in cytoplasm.  In this ,single molecule of glucose (6-c) is splitting into two molecules of pyruvate (3-c).  Glycolysis is actually a series of 10 chemical reactions that require the input of 2 ATP MOLECULES.  This input is used to generate 4 new ATP MOLECULES and NADH IS also produced.  In aerobic condition by glycolysis , cell produce pyruvate(32 ATP) or in anaerobic condition lactate (2 ATP).  Fermentation(DOES NOT REQIURE ENERGY) is also a ancient , major producing pathway that occurs in almost all cells .
  • 9.
  • 10.
  • 11. SECOND PROCESS IN THE EUKARYOTIC ENERGY PATHWAY  CITRIC ACID CYCLE or KREBS CYCLE or TRICARBOXYLIC ACID CYCLE(TCA cycle).  When the oxygen is available , the pyruvates produced by glycolysis become the input for the next portion of the eukaryotic energy pathway.  During this stage ,each pyruvate molecule in the cytoplasm enters the mitochondrion , where it is converted in to ACETYL CO-A.  ACETYL CO-A is a two –carbon energy carrier ,and the third –carbon combines with oxygen and it is released as carbon dioxide.  At the same time , an NADH carrier is generated.  Acetyl CO-A then enters a pathway called CITRIC ACID CYCLE.  IT is a 8 step chemical reaction, generates 3 more NADH molecules and 2 other carriers (FADH2 and GTP).  2-C ACETYL CO –A + 2-COXALOACETATE =6-C TRICARBOXYLIC ACID.  Total 24 ATP molecules are produced by this cycle.
  • 12. THIRD PROCESS IN THE EUKARYOTIC ENERGY PATHWAY  ELECTRON TRANSPORT CHAIN , catalyzed by several protein complexes located in the mitochondrional inner membrane. This process called OXIDATIVE PHOSPHORYLATION.  IT TRANSFERS ELECTRON from NADH AND FADH2. through the membrane protein complexes , ultimately to oxygen ,where they combines to form water.  As the electron , travel through the protein complexes in the chain , a gradient of hydrogen ions , or protons , forms across the mitochondrial membrane.  CELL used the energy of this proton gradient to create 3 additional ATP molecules for every electron that travels along the chain.  Together this processes occur in the mitochondria called RESPIRATION , a term used for processes that couple the uptake of oxygen and production of Carbon dioxide.
  • 13. BODY FLUIDS  Body is made up of solids and fluids. Fluid part is more than two third of the whole body. Water forms most of the fluid part of the body.  Total water in body is about 40L It is distributed into two major components:-  Intracellular fluid (ICF) :-22L in volume and is 55% of total body water.  Extracellular fluid (ECF) :-18L in volume and is 45%of total body water.
  • 15. ECF is divided into 5 subunits:  Interstitial fluid and lymph (20%)  Intravascular fluid / Plasma (7.5%)  Mesenchymal fluid / Fluid in dense connective tissues like cartilage (7.5%)  Fluid in bones (7.5%)  Transcellular fluid (2.5%) that includes: a) Cerebrospinal fluid b) Intraocular fluid c) Digestive juices d) Synovial fluids in joints e) Fluid in urinary tract d) Serous fluid- intrapleural fluid, pericardial fluid and peritoneal fluid.
  • 16.  ECF contains large quantity of sodium, chloride, bicarbonate, glucose, fatty acids and oxygen  ICF contains large quantity Potassium, Phosphate , magnesium, Small amount of sodium,chloride,  pH of ECF = 7.4 and pH ICF = 7.0
  • 17. Dehydration  State of deprivation of water. Corresponding loss of electrolytes’  Pathogenesis : decrease of body water decrease blood volume withdrawal of fluid from interstitial compartment with hyperosmolality . shifting of intercellular water to extracellular compartment resulting in cellular dehydration.  Causes Deficient water intake. e.g. dysphagia, starvation. Excessive loss of water. e.g. diabeties insipidus, pyrexia
  • 18. Applied physiology Dehydration  Dehydration is defined as the excessive loss of water from the body.  Daily water requirement is 1litre and for active individual 2-3 liters  Mild dehydration: fluid loss is about 5%of total body fluids  Moderate dehydration: fluid loss is about 10% of total body fluids  Severe dehydration: fluid loss is more than 15% of total body fluids.  Causes are:- severe diarrhea and vomiting, excess urinary output , insufficient intake of water, excess sweating, use of laxatives or diuretics.
  • 19. Water intoxication or Overhydration  Condition characterized by great increase in water content of the body.  Also known as hyperhydration , water excess or water poisoning.  When kidney have a restricted ability to dilute the urine.  when large amounts of pure water is given. It results in expansion of extracellular fluid compartment or sodium in your blood to drop too low (hyponatreima) with reduced osmolality and intracellular edema. Derangements in body fluids
  • 20. Causes :  a)Heart failure in which heart cannot pump blood properly.  b) Renal disorders.  c) Hypersecretion of anti diuretic hormone (vasopressin).  d) IV or oral administration of unduly large amount of medication and fluids. eg drugs containing estrogen , hormone replacement therepy , NSAID’S  e) Infants is first month of life as kidney is underdeveloped.  f) An adult whose liver and heart working normally can develop overhydration rarely if person consumes 8L water everyday regularly  g) Children having swimming practice.
  • 21. Edema  Abnormal or excessive collection of fluid in the interstitial tissue space and serous cavities.  Edema may be of different types: 1. Localized- Inflammatory , lymphatics , toxic , 2. allergy. 3. Generalized- renal , cardiac , nutritional. 4. Special- Pulmonary , cerebral.  Edema fluid can be : Transudate or Exudate.
  • 22.
  • 23. DISTUBANCES IN ELECTROLYTES  The pH of arterial plasma is normally 7.40 +0.5 or -0.5 and venous plasma is slightly lower.  Decrease in pH below normal is acidosis.  Increase in pH above normal is alkalosis.  It depends on : 1.concentration of bicarbonate ion. 2.pCO2 that determines concentration of bicarbonate.
  • 24. METABOLIC ACIDOSIS:  Fall in pH because of fall of bicarbonate ions and increased H+ ions . E.g. lactic acidosis , chronic renal failure.  This occurs when strong acids are added to blood. E.g. If large amount of acid is ingested. E.g. , in Aspirin overdose acids in blood are quickly increased lowering the available buffers. METABOLIC ALKALOSIS: Rise in pH due to rise in HCO3- level of plasma and loss of H+ ions . E.g. Severe and prolonged vomiting, Cushing’s syndrome .
  • 25.
  • 26. RESPIRATORY ACIDOSIS:  Fall in blood pH due to raised Pco2 as a consequence to under ventilation of lungs. E.g. Air obstruction in bronchitis, asthma. Rise in blood pH due to lowered Pco2 as a consequence to hyperventilation of lungs. E.g. Hysterical over breathing, working at high temperature, at high altitudes. RESPIRATORY ALKALOSIS
  • 27.
  • 28. Homeostasis  Homeo = same ; Stasis = standing.  ‘Homeostasis’ refers to maintenance of constant internal environment of the body.  In 19th century great biologist Claude Bernard said that multicellular organism including man live in a perfectly organized and controlled internal environment, which he called as ‘milieu interieur’.  The term homeostasis was coined by Harvard Professor, Walter B Cannon in 1930.
  • 29. Role of various system of the body in homeostasis  The ph of the ECF has to be maintained at the critical value of 7.4. Tissue cannot survive if this is altered. Decrease in ph is known as acidosis, or increase in ph is known as alkalosis. Respiratory system, blood and kidney help in regulation of ph.  Ideal body temperature is 37.5 degree Celsius. Alteration in this temperature alters metabolic activity of cell.  Skin, respiratory system, digestive system, excretory system, skeletal muscle and nervous system maintains the body temperature.
  • 30.  Nutrients are essential for variety of cells and growth of tissue. Nutrients must be digested, absorbed into blood and supplied to cells. Digestive and circulatory system play a major role in supply.  Adequate amount of oxygen should be supplied to cell as well as carbon dioxide and other waste products should also be removed. Respiratory system is involved in supply of oxygen and removal of carbon dioxide while kidneys and excretory
  • 31.  Hormones are essential for the metabolism of nutrients and other substance necessary for the cell. Endocrine system help to maintain the synthesis and release of appropriate amount of hormones.  Water and electrolyte balance should be maintained. Otherwise it will lead to dehydration, water toxicity and alteration in osmolality of body fluids. Kidney, skin ,salivary glands and GIT takes care of this.
  • 32. NORMAL WATER BALANCE  Average water intake is 2800 ml / day.  Water is eliminated from the body via kidney in the form of urine (1500 ml/day), via skin (800ml/ day), via lungs (400ml/day), via faces (100ml/day).
  • 33. NORMAL ELECTROLYTE BALANCE  A number of acids such as carbonic, phosphoric, sulfuric, lactic, hydrochloride, ketoacids are formed during normal metabolic activity.  Regulation of Acid Base Balance occurs with the help of a Buffer System.  Buffers are weak acids and strong bases which limit change in H+ ion concentration by taking up H+ when pH rises.  They form first line of defense in regulating pH.
  • 34. Interaction between extracellular and intracellular environment:  Cell membrane allows water & nonpolar molecules to permeate by simple diffusion cell membranes , however also have to allow passage of various polar molecule such as ions, sugars, amino acids, nucleotides and many cell metabolites.  Membrane proteins are responsible for this transferring of solute across cell membrane known as membrane transport proteins.
  • 35.  There are two major classes of proteins. -Carrier proteins -Channel proteins  The lipid bilayer cell membrane of cell is not miscible with either the extracellular fluid or the intracellular fluid.  Therefore, it constitutes a barrier against movement of water molecules and water-soluble substances between the extracellular and intracellular fluid compartments.
  • 37. Cell membrane transport: exchange mechanism  PASSIVE PROCESSES -Simple Diffusion -Facilitated Diffusion: Osmosis (require carrier protein)  ACTIVE PROCESSES -Active transport (require carrier protein and energy) -Vesicular or bulk transport 1. Exocytosis 2.Endocytosis ( Phagocytosis & Pinocytosis)
  • 38. Passive transport:  Transport along the concentration gradient or electrical gradient or both electrochemical gradient is called passive transport it is also known as diffusion or downhill transport.  It does not need energy.  It is of two types: - Simple Diffusion -Facilitated Diffusion
  • 39.
  • 40. SIMPLE DIFFUSION  Kinetic movement of molecules or ions occurs through intermolecular spaces without any interaction with carrier proteins in the membrane.  Diffusion rate is related to temperature, pressure, state of matter, concentration gradient, and surface area of membrane.  Rate of diffusion is determined by amount of substances available, the velocity of kinetic motion, number and sizes of opening in cell membrane through which molecule or ions can move.
  • 41. Simple diffusion can occur through cell membrane by two pathways: 1. Through interstices of lipid bilayer if the diffusing substance is lipid soluble. 2. Through watery channels that penetrate all the way through some of the large transport protein.
  • 42. FACILITATED DIFFUSION  Facilitated diffusion is the net movement of molecules from a high concentration to a low concentration with the aid of channel or carrier proteins.  Carrier proteins aids passage of the molecules or ions through the membrane by binding chemically with them and shuttling through the membrane.  E.g. Ions (Na+, K+, Cl-), Sugars (Glucose), Amino Acids, Small water soluble molecules, and water
  • 43. OSMOSIS  Osmosis is the net diffusion of water across a selectively permeable membrane from a region of high water concentration to one that has a lower water concentration. (Guyton A.C, Hall J.E- The Book of Medical Physiology. 11th edition)
  • 44. TONICITY  Tonicity refers to the total solute concentration of the solution outside the cell. There are three types of tonicity: 1. ISOTONIC: no net movement of water. 2. HYPOTONIC: cell gain water and swell. 3. HYPERTONIC: cell loose water and shrink.
  • 45. Active transport:  Movement of substances against the chemical or electrical or both (electrochemical) gradient is called active transport.  Also kas uphill transport.  It requires energy which is obtained by the breakdown of high energy compounds ATP.
  • 46.  Active transport is divided into two types according to the source of the energy used for transport: 1. Primary active transport: Energy is derived directly from breakdown of adenosine triphosphate (ATP) or of some other high-energy phosphate compound. 2. Secondary active transport: Energy is derived secondarily from energy that has been stored in the form of ionic concentration differences between the two sides of a cell membrane, created originally by primary active transport.
  • 47.  In both instances, transport depends on carrier proteins that penetrate through the cell membrane, as is true for facilitated diffusion.  However, in active transport, the carrier protein functions differently from the carrier in facilitated diffusion because it is capable of imparting energy to the transported substance to move it against the electrochemical gradient.
  • 48. Vesicular or bulk transport  Large particles and other substances can be moved between the external environment, the plasma membrane, and the interior of the cell via: a) Exocytosis b)Endocytosis -Phagocytosis -Pinocytosis
  • 49. Exocytosis  It is the process by which a vesicle moves from the cytoplasm to the plasma membrane where it discharges its contents to the extracellular space. There are two general pathways of exocytosis: 1. Constitutive pathway 2. Regulated secretory pathway
  • 50.  Constitutive pathway: continuous process where proteins are secreted immediately after their synthesis, as seen in the secretion of immunoglobulins by plasma cells and of tropocollagen by fibroblasts.  Regulated secretory pathway: proteins are concentrated and transiently stored before they are excreted out of the cell, as seen in the release of zymogens granules by chief cells of the gastric mucosa and by acinar cells of the pancreas.
  • 51. Endocytosis:  Movement of large molecules into the cell by engulfing them in vesicles, using ATP energy is known as endocytosis.  It can be of two types: 1. Phagocytosis 2. Pinocytosis
  • 52. PINOCYTOSIS PHAGOCYTOSIS 1.It is the bulk intake of fluid material by a cell. 1. It is the intake of solid material from outside to inside of cell. 2.Vesicles are small 100-200 nm in diameter. 2. Vesicles formed are large, 1-2μm in diameter. 3.Membrane possesses receptor pits for receiving the materials. 3. Receptor pits are absent. 4.Digestion or breakdown of absorbed food may or may not occur. Accordingly a food vacuole may or may not formed. 4. A digestive or food vacuole is formed from a phagosome. 5.Lysosomes play no role in utilization of absorbed materials if digestion is not involved. 5. Lysosomes are essential because solid substance taken in by phagocytosis require digestion. 6. There is no exocytosis 6. The undigested parts of the solid materials are thrown out by exocytosis .
  • 53. (Guyton A.C, Hall J.E- The Book of Medical Physiology. 11th edition)
  • 54.
  • 55. CELL JUNCTIONS  When cell come into contact with one another, sometimes with the extracellular matrix specialized junctions may form at specific sites on contacting cell membrane.  Cell junction is also known as intercellular bridge.  These are abundant in epithelial tissues.
  • 56. SPECIALIZED JUNCTION MAY BE CLASSIFIED INTO SEVERAL DIFFERENT CATEGORIES:  OCCLUDING (TIGHT) JUNCTIONS/ZONULA OCCLUDENS  ADHESIVE JUNCTIONS 1. Cell-to-cell Zonula adherens Macula adherens (Desmosomes) 2. CELL-TO-MATRIX Focal adhesions Hemidesmosomes  COMMUNICATING (GAP) JUNCTIONS
  • 57.
  • 58. Occluding junctions/ Tight junctions/ Zonula Occludens ● Opposing cell membrane are held in close contact by the presence of transmembrane adhesive proteins arranged in anastomosing strands that encircle the cell. ● Intercellular space is obliterated at the tight junctions. ● Transmembrane adhesive proteins are: -Occludin -Members of Claudine family -
  • 59.
  • 60.  Several cytoplasmic proteins associated with intercellular portion of transmembrane proteins like: -cell polarity related proteins -vesicular transport related proteins -kinases -transcription factors -tumour suppressor protein  Some cytoplasmic protein of tight junction bind to actin filaments.
  • 61.  BARRIER FUNCTION: Tight junctions controls the passage of materials through the intercellular spaces (from interstitium to the lumen of the gland).  MAINTAINENCE OF CELL POLARITY: Fencing function maintain two major domains of the cell membrane by keeping proteins in apical region. -Apical surface -Basolateral surface
  • 62.  FENCING FUNCTION: Tight junction prevents lateral movement of proteins and lipids in cell membranes thus, act as a fence . Due to this it is sometimes referred as impermeable junction.  Tightness of junction is specifically related to claudin and is correlated with number of strands of transmembrane proteins.  BLOOD BRAIN BARRIER: These are present in brain capillaries and forms the blood brain barrier, which prevent the entry of many substances into brain and allows only lipid soluble substances like drugs and steroid hormone to enter into brain.
  • 63. ● Tightness of junction is specifically related to claudin and is correlated with number of strands of transmembrane proteins. ● Tight junction joining salivary glands secretory cells have only 2 or 3 Junctional strands and are relatively permeable to water , whereas those joining salivary gland striated duct cells may have 6 to 9 strands and are relatively impermeable to water. The permeability of tight junctions in some tissue may be regulated by certain neurotransmitter and hormones.
  • 64. Current model of tight junctions: MOLECULAR BIOLOGY OF CELL 3rd edition ALBERT BRAY LEWIS RAFF ROBERTS WATSON ● It is postulated that the sealing strands that hold adjacent plasma membranes together are formed by Continuous strands of transmembrane Junctional proteins, which make contact across the intercellular space and create a seal.
  • 65. Leaky tight junctions: In some situations occlusion of the gaps between the adjoining cells may be incomplete and the junction may allow slow diffusion of molecules across it. These are referred to as leaky tight junctions.
  • 66. Applied physiology: disease caused if protein encoding for tight junctions are mutated.  Hereditary deafness  Ichthyosis (genetic disorder –dry, scaly, thickened skin)  Sclerosing cholengitis (inflammation of bile duct causing obstruction)  Hereditary hypomagnesemia  Synovial sarcoma (soft tissue cancer)
  • 67. ADHESIVE JUNCTIONS ● These junctions hold the cells together or anchor cells to extracellular matrix. ● Intercellular space is maintained at ~ 25nm-30 nm ● Important in cellular signalling.
  • 68. ● Their cytoplasmic components may interact with the cytoskeleton, triggering changes in cell shape or motility or with certain tumor suppressor molecule or may act as nuclear transcription factors or co activators. ● Sometimes loss of cell-cell or cell-matrix contact may lead to apoptosis . Whereas in other cases loss of contact may lead to loss of polarity & differentiation or unregulated cell proliferation.
  • 69. They are of 2 types of adhering junctions:  a. Cell to cell: -Zonula Adherens -Macula Adherens (Desmosomes)  b. Cell to matrix: Hemi-Desmosomes
  • 70. Zonula adherens  Cell–to–cell adherens junction in epithelial sheets often forms a continuous adhesion belts k/as zonula adherens around each of the interacting cells in the sheets located near the apex just below the tight junctions.  The adhesion belt in adjacent epithelial cells are directly opposed and the interacting plasma membrane are held together by membrane linker protein that are members of calcium dependent cell-cell adhesion molecule called cadherins.
  • 71.  Cytoplasmic adapters of cadherins : E cadherins, alpha and beta catenins  Cytoskeletal components: Actin filaments  Other: Nectin – it establishes initial adhesion site for e-cadherins and other protiens.  Sites: Adherens junctions are present in the intercalated disks in heart between the branches of cardiac muscles. During the contraction and relaxation of heart, cardiac muscle fiber are held together by means of this junction. Adherens junction in skin helps to withstand mechanical stress.
  • 72. Diagram showing molecular structure of adhering junction.  Cadherins are Membrane linker proteins.  Cytoplasmic adapters are Catenins alpha and beta. They interact with Cytoplasmic domain of cadherin.  Cytoskeletal component are Actin filaments.  Nectin is initial adhesion site E-cadherins & other proteins.  P120 catenin stabilize the junction. Affadin links nectin to actin filament. Alpha actinin & ponsin links affadin and Vinculin. Ten Cate’s
  • 73. Macula adherens /desmosomes  Desmosomes is a cell-cell junction , where intermediate filament connect two adjacent cells to form continuous network through out the tissue.  Also called macula adherens.  These are button like points of intercellular contact that rivets cell together.  Intermediate filaments are attached with thickened patches.  Some of these filaments are parallel to membrane others are arranged in radiating fashion.
  • 74.  The transmembrane protein present mainly belong to cadherin family of calcium dependent cell-cell adhesion molecule.  The cadherins are desmoglein and desmocollin. The interaction of these transmembrane protiens with those of the adjacent cells results in dense line in middle of intercellular space at the desmosome.  Catenins are desmoplakin, plakoglobin, plakophilin. These form electrodense plaque on cytoplasmic side of desmosome. These plaque serve as attachment site for cytoskeletal component which are intermidiate filaments.
  • 75. Desmosome in gingival epithelium  Cohesion between merkel cells and between stratum spinosum of keratinized gingival epithelium is provided by desmosomes.  A desmosome may be considered to be 2 hemidesmosomes facing one another, separated by a zone containing electron dense granulated material (GM).
  • 76. Thus a desmosome comprises the following structural components: 1. The outer leaflets (OL) of the cell membrane of two adjoining cells. 2. The thick inner leaflets (IL) of the cell membranes. 3. The attachment plaques (AP) which represent granular and fibrillar material in the cytoplasm. The presence of a large number of desmosomes indicates that the epithelial cells are solid.
  • 77. Clinical Periodontology and Implant Dentistry by Jan Lindhe , 5th edititon
  • 78.  This is the diagram from the stratum basale to the stratum granulosum.  Both the no of tonofilaments (f) in the cytoplasm & no of desmosomes (D) increases.  No of organelles such as mitochondria (M), lamellae of RER (E) , golgi complexes (G) decreases in keratinocytes on their way from basal cell layer to surface.  In stratum granulosum, electron dense keratohyline bodies & clusters of glycogen containing granule start to occur
  • 79. Applied physiology:  The importance of desmosomes in holding cells together is demonstrated by form of potentially fatal disease, pemphigus. In which individual make antibodies against one of their own desmosomal cadherin protiens these antibodies binds to and disrupts desmosomes between skin epithelial cells causing severe blistering as a result of leakage of body fluids into loosened epithelium.
  • 80. Hemidesmosomes (cell-matrix junction)  They are the variant of the spot like adhering junctions, has the structure of only half a desmosome.  This type of junction bonds epithelial cells to their underlying basement membrane and is well developed under the basal layer of the epidermis.  Protiens involved are mainly integrins.
  • 81. Interface between basal cells of gingival epithelium and basal lamina or basement membrane facing connective tissue BC: basal cell LL: lamina lucida LD: lamina densa HD: hemidesmosome AF: anchoring fibres CT: cytoplasmic tonofilaments (Clinical Periodontology and Implant Dentistry by Jan Lindhe , 5th edititon)
  • 82. Interface between junctional epithelium and tooth  E: enamel  1: space between JE & E, continuation LD in the basement membrane of the connective tissue side.  2: continuation of LL LL: lamina lucida LD: lamina densa AF: anchoring fibres (Clinical Periodontology and Implant Dentistry by Jan Lindhe , 5th edititon)
  • 83. Epithelial rests are surrounded by a distinct basal lamina, and are interconnected by hemidesmosomes and contain tonofilaments (Clinical Periodontology and Implant Dentistry by Jan Lindhe , 5th edititon)
  • 84. Applied physiology:  Like desmosomes some , the adapter proteins , bullous pemphigoid antigen 230 (BP230) & plectin , form a dens plaque on the cytoplasmic surface of hemidesmosomes which functions as the attachment site for intermediate filaments.
  • 85. Communicating /Gap junction  Gap junctions are plaque like regions of cell membrane where intercellular space narrows to 2 nm to 3 nm & transmembrane protiens of connexin family forms aqueous channels between the cytoplasm of adjacent cells.  Permeability properties of a gap junction depends on the distribution of specific proteins in specific tissues. (Ten cate’s)
  • 86.  6 connexin molecule forms a connexon which has a central channel of 2 nm in diameter.  Connexon in one cell gets paired with the connexon of adjacent cell to create a patent channel.  Small molecule like ions and signalling molecules can move readily from one cell to another & allows coordinated response to the stimulus by the cells that are interconnected.
  • 87.  These channels in the gap junction enable ions and small molecules including amino acids, sugars, nucleotides, and steroids to pass directly from one cell to another without the need for such constituents to enter the intercellular space.  Gap junctions are important where rapid communication between adjacent cells is required as in smooth and cardiac muscles.  In smooth muscles: gap junction is called a nexus. Ten cate’s
  • 88.  In cardiac muscles: gap junction forms a part of intercalated disc.  Diameter of the channel is controlled by the calcium level , if clalcium level increases the diameter decreases and if calcium level decreases diameter increases.  Diameter also depends upon pH , electrical potential , hormones and neurotransmitters.
  • 89. Gap junction diagram &electron micrographs  Single connexon consists of 6 connexin molecule.  Central channel Is aopproximately 2nm in diameter.
  • 90. Applied physiology: Mutations in genes coding for connexins may cause:  Deafness  Keratoderma (thickening of skin on palms and soles)  Cataract  Peripheral neuropathy  Heterotaxia (abnormal arrangements of right and left symmetry of body organs or parts).
  • 91.
  • 92.
  • 93. Conclusion:  Cells in tissues are linked to one another and to the extracellular matrix at specialized contact sites called cell junctions. Thus , becoming chemically and electrically coupled.  As long as normal conditions are maintained in the internal environment , cell of the body continuous to live and function properly.  Each cell contributes in homeostasis & each cell benefits from homeostasis in turn . This reciprocal interplay provides continuous automaticity to the body . If it is disturbed then all cells suffer.
  • 94. References  Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson J.D- Molecular Biology of The Cell, 3rd edition.  Guyton A.C, Hall J.E- The Book of Medical Physiology, 11th edition.  Kim E.Barrett, Susan M.Barmun, Scott Boitano, Hedwnn L.Brook’s GANONG’S REVIEW OF MEDICAL PHYSIOLOGY, 23rd edition  K.SEMBULINGAM Essential Of Medical Physiology  Molecular and Cell biology of the Gingiva, PERIODONTOLOGY 2000, VOL 24, PG 28-55  Essentials of cell biology ,book by alexander johnson , dennis bray, julian lewis and peter walter