Lecture 5 Connective Tissue & ECM Flashcards
Extracellular matrix (ECM)
Cells are of mesodermal origin
ECM contains:
Fat cells
Fibrocytes (inactive) fibroblasts (active)
Lymphocytes
Macrophages
Melanocytes
Mast cells
Capillaries
Collagen fibres
Connective tissue fibres
Reticular fibres
Connective tissue
Composed of
CELLS:
Mobile -
blood cells red (O2)
white (immune cell)
Fixed-
adipocytes (store fat)
Macrophages (sometimes mobile)
Fibroblasts which synthesize the matrix
MATRIX:
Ground substance:
Mineralised
- bone
Gelatinous
- loose connective tissue
-dense connective tissue
- cartilage
-adipose tissue
Watery
-blood plasma
Protein fibres:
Fibronectin- connects cells to matrix
Fibrillin - forms filaments & sheets
Elastin- stretch and recoil
Collagen - stiff but flexible
Fibronectin
A multifunctional glycoprotein that mediates adhesion between a wide range of cells and ECM components
Reshaping a cell
Distorts it’s nucleus which can in turn affect the structure and physiology and polarity of the cell
Stem cells grown
On hard structure : become bone
On soft structure: become fat cells
Connective tissue disorder/disease
Marfan syndrome - fibrillin distortion
Scurvy
Hypermobility
Connective tissue functions
Form and support - bone/cartilage
Physical barrier
Connects and anchors parts
Medium for exchange of nutrients - oxygen carbon dioxide and waste products
Aids defence and protection
Cushioning and thermoreg
Signalling, ageing and stem cell biology
Types of connective tissue
Loose connective tissue e.g. dermis under epithelia
Dense irregular connective tissue - muscle and nerve sheets
Dense regular connective tissue -
Tendons and ligaments
Blood
Cartilage
Bone
Connective tissue classification
Proper:
Loose and dense regular/irregular
Specialised:
Bone, cartilage, adipose, blood, haemopoietic tissue, lymphatic tissue
Loose connective tissue function
Flexible tissue with multiple cell types and fibres
EXCHANGE OF SUBSTANCES
Collagen fibres thin and sparse
ECM occupies greater volume than fibres
Viscous but permits diffusion
O2 and nutrients FROM small vessels
CO2 and metabolic waste To small vessels
DEFENCE
Adjacent to epithelia of body surface and beside internal organs
Initial site of defence against pathogens when an epithelium is breached
In response to specific stimuli will contain wandering cells of the immune system from local blood vessels
Can undergo swelling for inflammatory/immune response
In areas potentially exposed to a lot of pathogens, large populations of immune cells maintained in loose connective tissue called lamina propria : in gut and respiratory epithelium.
Fibroblasts need to be stretched to secrete collagen
Characteristics of dense irregular tissue
Mostly consists of collagen fibres
Little ECM
Provides significant strength
Collagen fibres arranged in bundle in various orientations hence ‘irregular’
Specific types:
Intestinal submucosa - resists stretch and distension by gut contents
Reticular or deep layer of dermis - resists stretching forces from exterior
Characteristics of dense regular tissue
Mainly collagen fibres little ECM
Fibres aligned in parallel array hence ‘regular’
Main constituent of ligaments, tendons and aponeuroses
Ligaments - bone to bone
Tendons - bone to muscle
Aponeuroses - tendons for muscle sheets e.g. Rectus abdominus “six pack”
Cornea of eye
Tendons
Parallel bundles of collagen fibres (65-80%) with rows of fibroblasts (tendinocytes or tenocytes) in between
1-2% elastic fibres - can barely stretch
Tendinocytes - secrete an ECM that mechanically isolates them from load bearing collagen fibrils
Tendon as a whole surrounded by a connective tissue capsule which often extends into tendon, partitioning it into subsections called fascicles
Epitendinium - Outer capsule collagen fibres less regularly orientated
Endotendinium - Connective tissue partitioning in the tendon, also contains nerves and blood vessels
Ligaments and aponeuroses
Ligaments: contain fibres and fibroblasts in parallel
Fibres less regularly orientated than in tendons
Mostly collagen, some associated with nervous system mainly consist of elastic fibres (elastic ligaments)
Aponeuroses - broad flattened tendons
Have collagen fibres arranged in layers with fibres in adjacent layers at 90° to each other - orthoganol array
Cornea of eye organised this way - important for transparency
Support tissues
Connective tissues
Connective tissue fibres:
Produced by fibroblasts - collagen, reticular,elastin, fibrillin, fibronectin
ECM - ground substance and fibre
Connective tissue cells
When fibrillin is pulled it can determine how much growth hormone is released
Collagen fibres and fibrils
Most abundant fibre type
Flexible, high tensile strength
>20 types of collagen
Fibres made up of threadlike subunits - collagen fibrils
Diameter of collagen molecule (tropocollagen) varies from 10-300nm
It is 300nm long and 1.5nm thick in dense regular connective tissue or tendons
3 polypeptides form triple helix
15-20nm diameter in developing/immature tissue
Individual fibres are straight but may be arranged in an overlapping network (as in bone)
Reticular fibres
Composed of Type ll collagen
20nm wide
Branched
Arranged in a network
Found
at boundary of connective tissue and epithelium
Around adipocytes (fat cells), small blood vessels, nerves and muscles
Supporting stroma of hemopoietic and lymphoid tissues but not in thymus
May be a sign of tissue immaturity
Embryonic
Initial stages of wound healing and scar formation, providing quick strength - over time replaced with stronger collagen l type fibres
Elastin- fibres
Thinner than collagen fibres and coiled
Linked by cov links to other elastin fibres producing a 3D meshwork
Interwoven with collagen fibres to prevent tearing by limiting distensibility
Produced by fibroblasts and smooth muscle
Central core of elastin surrounded by fibrillin and microfibrils
Fibrillin microfibrils form first and provide a template for elastin deposition
In absence of fibrillin get elastin sheets or lamellae e.g. blood vessel walls
The ECM
Diff proportions of ECM components secreted by diff tissues gives rise to diff properties
Provides mechanical and structural support and tensile strength
Biochemical barrier
Regulated activity of cellular component
Anchors cells
Cellular migration pathways in development and repair
Binds and retains growth factors
Includes fibrous proteins, proteoglycans and glycoproteins (e.g. fibronectin and laminin)
Lost in most routine histological procedures - only cells and fibres retained
Ground substance
Found between cells and fibres of connective tissue
Gel-like consistency with high water content
Composed of
Proteoglycans- proteins linked to heteropolysaccharides e.g. GAGs
Gylcosaminoglycans (GAGs e.g. hylauronic acid)
Glycoproteins (e.g. fibronectin, laminin, tenascin and osteopontin)
Allows diffusion if nutrients and oxygen between cells and blood vessels
Glucosaminoglycans (GAGs)
Glucosaminoglycans (GAGs)
Unbranched large polysacc
(70-200 residues)
Neg charged
Hydrophilic, form hydrated gel
E.g. Hylauronic acid (not protein linked)
Chondroitin sulphate and dermatin sulphate
Heparan sulphate and heparan
Keratan sulphate
Covalent link to core protein
Combination is a proteoglycan
Proteoglycan aggregates
Hylauronan is an unbranched free carbohydrate chain.
Link proteins attach proteoglycan monomers to form proteoglycan aggregates.
Hylauron also binds to growth factors such as TGF beta
Multi adhesive glycoproteins
Bind to cell surface proteins and ECM components
Able to bind multiple substances
- fibronectin (20 types) can bind the cell surface receptor integrin and ECM components heparan sulphate, collagen types 1-3, hylauronan
-laminin (>15 types) binds integrins, heparan sulphate, type lV collagen and enactin
Cellular components of connective tissue : fixed
Fixed:
Fibroblasts - synthesise collagen, elastin and ground substance components
Myofibroblasts - synthesise fibres and ECM for wound healing
Macrophages- phagocytes
Adipose cells - lipid storing, hormone synthesis, growth factors
Mast cells - immune cells in skin and mucous membranes
Mesenchymal cells
Have potential to give rise to differentiated cells in tissue repair
- chondrocytes - secrete cartilage ECM
- osteoblasts - secrete bone ecm
Cellular components of connective tissue : wandering
Lymphocytes - immune
Plasma cells - produce antibodies
Philes - migrate from blood to connective tissue
Neutrophiles - phagocytes
Eosinophiles - allergic response
Monocytes - develop to macrophage
Basophiles - similar to mast cells
Myofibroblasts
Contain contractile machinery and rough ER
Similar to smooth muscle cells, possess gap junctions but exist as single cells and do not have a basal or external lamina
Involved in wound contraction causing wounds to close
May be fibroblasts modified as a result of stimuli associated with wound damage and repair
Immune system components in connective tissue
Macrophages
Phagocytose foreign material and present antigens to other cells e.g. T helper cells
Mast cells
Respond to antigens which the body has previously been exposed to “sensitisation”
Release granules containing substances which promote inflammation and immune response e.g. increase permeability of small blood vessels
Lymphocytes
