Introduction to yr3

1
Tissues all you ever wanted to know
adeel.iqbal_at_imperial.ac.uk
2
Content
Geared to tackle bulky marker questions! Imperial
College Structure Epithelial CellsEpithelial
TissuesExtracellular MatrixConnective
TissuesFluid Compartments of the
bodyNerveMuscleSignalling Between Cells I
Signalling Between Cells II
3
Content
Geared to tackle bulky marker questions!
4
Content

• Geared to tackle bulky marker questions!
• Cell Types and Cell Junctions
• Collagen Synthesis
• Proteoglycans
• Neuromuscular Tissue
• Smooth Muscle
• Cellular Signalling.

5
Tissues
Histology Histopathology
6
Content

• Geared to tackle bulky marker questions!
• Cell Types and Cell Junctions
• Collagen Synthesis
• Proteoglycans
• Neuromuscular Tissue
• Smooth Muscle
• Cellular Signalling.

7
Main Cell Types

• Epithelial cells cells forming continuous
  layers, these layers line surfaces and separate
  tissue compartments
• Mesenchymal cells cells of the connective
  tissues, e.g. fibroblasts (many tissues),
  chondrocytes (cartilage), osteocytes (bone),
  muscle cells (skeletal, cardiac, smooth)
• Haematopoietic cells blood cells and the cells
  of the bone marrow from which they are derived.
• Neural cells cells of the nervous system having
  two main types neurones (carry electrical
  signals) and glial cells (support cells)

8
Cell Junctions

• Most Apical to Basal
• Tight Junctions
• Adhesion Belts
• Desmosomes
• Gap Junctions

9
Cell Junctions
Tight Junctions Known as zona occludens. Most
apical. Prevent paracellular transport. Maintain
distinct basolateral and apical protienacious
composition.
10
Cell Junctions
Tight Junctions Known as zona occludens. Most
apical. Prevent paracellular transport. Maintain
distinct basolateral and apical protienacious
composition.
Adhesion Belt Also zonula. Just basal to tight
junction. Cadherin associated with actin
cytoskeleton. The control Junction
11
Cell Junctions
Tight Junctions Known as zona occludens. Most
apical. Prevent paracellular transport. Maintain
distinct basolateral and apical protienacious
composition.
Adhesion Belt Also zonula. Just basal to tight
junction. Cadherin associated with actin
cytoskeleton. The control Junction
Desmosomes Macula. Spotted adhesive molecules.
Resist shearing of cells. Hemidesmosomes link ECM
12
Cell Junctions
Tight Junctions Known as zona occludens. Most
apical. Prevent paracellular transport. Maintain
distinct basolateral and apical protienacious
composition.
Adhesion Belt Also zonula. Just basal to tight
junction. Cadherin associated with actin
cytoskeleton. The control Junction
Desmosomes Macula. Spotted adhesive molecules.
Resist shearing of cells. Hemidesmosomes link ECM
Gap Junctions Macula. Made of six subunits
permeation of ionic charge cause adjacent
activation. Homo or hetrohexamers of connexin.
13
Questions?
14
Content

• Geared to tackle bulky marker questions!
• Cell Types and Cell Junctions
• Collagen Synthesis
• Proteoglycans
• Neuromuscular Tissue
• Smooth Muscle
• Cellular Signalling.

15
The synthesis of type I collagen
Type I collagen is the most abundant protein in
the body - a major constituent of bone, skin,
tendon and cornea
16
Molecular Constitution of Collagens

• Over 20 collagen types are known, designated by
  roman numerals
• Each collagen molecule comprises three ? chains.
• Type I collagen has chains from two different
  genes - its composition is ?1(I)2 ?2(I)
• Types II and III collagen have only one chain -
  their compositions are, therefore, ?1(II)3 and
  ?1(III)3
• There are over 25 genes encoding collagens in
  mammals

17
Synthesis
Collagen ? chain mRNA
18
Collagen synthesis in the rough endoplasmic
reticulum
Ribosome omitted for clarity
19
The collagen triple helix
The gly-x-y repeat x is often proline, y is
often hydroxyproline
Three ? chains forming a triple helix glycine
is the only amino acid small enough to occupy the
interior.
Each ? chain is approximately 1000 amino acids,
forming a left-handed helix
20
Lysine and proline hydroxylation
Prolyl and lysyl hydroxylases require Fe2 and
vitamin C
Contribute to interchain hydrogen bond formation.
Lysine and hydroxylysine are also modified in
the formation of covalent crosslinkages. This
takes place only after the collagen has been
secreted.
OH
OH
21
Fibrillar Collagen Assembly
tropocollagen
22
The ¾¼ stagger gives tensile strength
Electron micrograph of a negatively stained
collagen fibril
23
Questions?
24
Covalent cross-links provide tensile strength and
stability
The copper requiring lysyl oxidase is the only
known enzyme involved. It acts on both lysine
and hydroxylysine residues. The type and extent
of cross-links is tissue specific and changes
with age.
25
Content

• Geared to tackle bulky marker questions!
• Cell Types and Cell Junctions
• Collagen Synthesis
• Proteoglycans
• Neuromuscular Tissue
• Smooth Muscle
• Cellular Signalling.

26
Proteoglycans
Core protein to which one or more
glycosaminoglycan chains are covalently attached
Glycosaminoglycans are long, unbranched sugars
consisting of repeating disaccharides
27
Proteoglycans
Core protein to which one or more
glycosaminoglycan chains are covalently attached
Glycosaminoglycans are long, unbranched sugars
consisting of repeating disaccharides
There are several proteoglycan families based on
structural and functional characteristics Aggregat
ing (interact with hyaluronic acid) eg
aggrecan Small leucine rich eg decorin Basement
membrane eg perlecan, agrin Cell surface eg
syndecans 1-4
28
aggrecan
CS- chondroitin sulphate, KS- keratan sulphate
decorin
syndecan
DS- dermatan sulphate
HS- heparan sulphate
29
The linkage between a glycosminoglycan and the
core protein of a proteoglycan
Nearly always followed by a glycine residue
30
Glycosaminoglycan structure Dermatan sulphate
Chondroitin sulphate has glucuronic acid in place
of iduronic acid
31
Glycosaminoglycan structure- Chondroitin sulphate
Glucuronic acid
Chondroitin sulphate has glucuronic acid in place
of iduronic acid
32
Hyaluronan (a GAG)

• Distinct features
• Synthesized at the cell surface, not in the
  e.r./golgi
• No core protein
• Unsulfated

33
Structure of Aggrecan - a major cartilage
matrix constituent

• Chondroitin sulfate attachment region

Keratan sulfate attachment region
Hyaluronic acid binding region Link protein
Hyaluronic acid
34
Decorin-null mouse skin collagen
Wild type mouse skin collagen
35
Questions?
36
Content

• Geared to tackle bulky marker questions!
• Cell Types and Cell Junctions
• Collagen Synthesis
• Proteoglycans
• Neuromuscular Tissue
• Smooth Muscle
• Cellular Signalling.

37
(No Transcript)
38
bone
tendon
Skeletal Muscle - tissue components
fascicle
nerve
muscle fibre
blood vessels
39
Activation and relaxation (turning contraction
on and off)
40
Muscle fibre
41
(No Transcript)
42
Muscle fibre - closer look
myofibrils
43
Muscle fibre - closer look
Triad terminal cistern t-tubule terminal
cistern
44
Surface membrane
T-tubule
SR terminal cistern
Ca2
SR
Activation 1.action potential in sarcolemma and
T tubule 2. causes release of Ca from terminal
cisterns of SR 3. Ca binds to filaments and
permits crossbridge attachment 4. Ca actively
transported back into the SR (ATP driven pump)
Relaxation 1,2 3 stop, and 4 continues Ca
actively transported back into the SR (ATP driven
pump)
45
Contractile filaments force and movement
46
Contractile filaments produce force and sliding
myosin
crossbridge
47
Polymerisation of thick filaments
The structure of myosin filaments
Tail diameter 2 nm Thick filament backbone
diameter 16.3 nm Thick filament and packed
myosin heads 20.3 nm Length of native thick
filaments 1.6 µm
48
Structure of a sarcomere
Thick filament length 1.6 µm Containing 294
myosin molecules (588 heads). 3 myosins/crown,
spaced at 14.3 nm interval. Thin filament
length 1.1 µm. Length regulated by nebulin and
tropomodulin Titin is a large elastic and
extensible protein that links the thick
filaments to the Z-line, thus ensuring that the
thick filaments remain centred in the
sarcomere. Z-band width 0.052 µm in Type II
fibres, 0.101 µm in Type I fibres. Bare zone
0.15 µm wide D. A. Riley et al., (2002) Thin
filament diversity and physiological properties
of fast and slow fiber types in astronaut leg
muscles. J. Appl. Physiol. 92 817-825.
49
Sliding filament hypothesis
The filaments are stiff and largely inextensible.
Muscle shortening is brought about by the
interaction of myosin 'cross-bridges' interacting
with the thin (actin) filaments, which cause
changes in the overlap between the sets of
inter-digitating filaments. Myosin
cross-bridges are independent force generators.
Huxley, Brown Holmes 1965 Nature 206 1358
50
How much force?
Motoneuron
Motor unit a motoneuron and all the muscle
fibres it innervates (has synapses with). The
functional unit of normal skeletal muscle.
1)Recruitment - vary the number of motor units
that are active (and thus vary force).
51
How much force from each motor unit?
2) Frequency of stimulation number of attached
crossbridges depends on the concentration of Ca
around the filaments.
3) Overlap of the filaments number of
crossbridges that can attach.
4) Velocity of filament sliding when faster
there is less chance of attachment.
52
Comparison with other muscle types
53
Cardiac muscle fibres
54
Cardiac muscle structure and function
Striated - contractile mechanism as in skeletal
muscle
Each cell is small
Action potentials spread from cell to cell
Specific cells types are spontaneously active
Action potential shape and duration varies
between cell types
Functions as a pump by contracting and relaxing
rhythmically
55
Polymerisation of thick filaments
The structure of myosin filaments
Tail diameter 2 nm Thick filament backbone
diameter 16.3 nm Thick filament and packed
myosin heads 20.3 nm Length of native thick
filaments 1.6 µm
56
Structure of a sarcomere
Thick filament length 1.6 µm Containing 294
myosin molecules (588 heads). 3 myosins/crown,
spaced at 14.3 nm interval. Thin filament
length 1.1 µm. Length regulated by nebulin and
tropomodulin Titin is a large elastic and
extensible protein that links the thick
filaments to the Z-line, thus ensuring that the
thick filaments remain centred in the
sarcomere. Z-band width 0.052 µm in Type II
fibres, 0.101 µm in Type I fibres. Bare zone
0.15 µm wide D. A. Riley et al., (2002) Thin
filament diversity and physiological properties
of fast and slow fiber types in astronaut leg
muscles. J. Appl. Physiol. 92 817-825.
57
Sliding filament hypothesis
The filaments are stiff and largely inextensible.
Muscle shortening is brought about by the
interaction of myosin 'cross-bridges' interacting
with the thin (actin) filaments, which cause
changes in the overlap between the sets of
inter-digitating filaments. Myosin
cross-bridges are independent force generators.
Huxley, Brown Holmes 1965 Nature 206 1358
58
Composition of the Main Fluid Compartments
Extracellular fluids Plasma is like interstitial
fluid (IF) except plasma has more protein
Example of intracellular fluid
59
Questions?
60
Content

• Geared to tackle bulky marker questions!
• Cell Types and Cell Junctions
• Collagen Synthesis
• Proteoglycans
• Neuromuscular Tissue
• Smooth Muscle
• Cellular Signalling.

61
Smooth muscle
Cells appear smooth (not-striated) in
micrographs. Contain filaments, but they are not
arranged in regular arrays. Contractile
mechanism similar to skeletal and cardiac muscle
nucleus
smooth muscle fibre
autonomic neuron
62
Smooth muscle

• Cells are very small compared to skeletal and
  cardiac cells.
• Arranged in sheets forming walls of tubular
  organs
• blood vessels,
• gastro-intestinal tract
• reproductive tract, etc.

63
Smooth muscle
Activation mechanism varies between tissues

• Spontaneously active
• Stimulated/relaxed by
• neurons
• hormones
• stretch
• local factors - metabolites, nitric oxide,
  etc

64
Questions?
65
Content

• Geared to tackle bulky marker questions!
• Cell Types and Cell Junctions
• Collagen Synthesis
• Proteoglycans
• Neuromuscular Tissue
• Smooth Muscle
• Cellular Signalling

66
Thank YouTo Download This Lecture Please Visit
Our Website

• union.ic.ac.uk/medic/muslim