extra cellular matrix Flashcards
what is ecm
- network of macromolecules that occupy extra cellular space eg. proteins, proteoglycans, minerals
- secreted by cells
- forms large % of connective tissue
what two main classes of macromolecules does the ECM of connective tissue
- fibrous proteins
- proteoglycans
- water is also a major component
what are 5 roles of ecm
- acts as a signal which influences cell function
- stores and presents growth factor
- acts as a scaffold for tissue repair
- important in cell adhesion
- establishes tissue microenvironment
ecm proteins - collagen
- collagen is the most abundant protein in ecm
which two collagen types are the most abundant in ecm of connective tissues
- type 1 and type 11 such as tendons, cartilage and bone
properties of type 1 and type 11 collagen
- resist stretching and provide a structural framework and tissue strength to the tissues (tensile properties)
how many types of collagen
- type 1, 2, 3, 4 (basal lamina - non fibrular) , 5 (less abundant)
elastin properties
- low tensile strength
- elasticity found in tissues such as lungs and arteries - this allows for them to be repeatedly stretched and undergo elastic recoil
what is fibronectin and its role
- fibrous proteins found in ecm
- has 2 forms; soluble form in blood, insoluble in cell
- large dimer of 2 nearly identical proteins
- main role in guiding the organisation and structure of ecm
what is laminin and its role
- trimeric cross structure - sheet like
- binding site for cells and other proteins
- major component of basal lamina
- mutations - nephrotic syndrome (kidney disease issue with filtration)
what roles are both laminin and fibronectin involved in
- cell differentiation
- cell migration
- cell adhesion
- they both can bind to both components of the ECM and intern receptors on plasma membrane of cells so anchoring the cell directly to ecm
what are proteoglycans
- composed of a specific protein core structure to which long, unbranched polysaccharide chains are covalently attached
what is a glycosaminoglycan (GAG)
- the polysaccharide side chains attached to the core protein are made up of repeating disaccharide units and are named glycosaminoglycans
some proteoglycans
- contain one or two GAG and some have over 100
- some GAG eg. keratin sulphate found in aggrecan are sulphated
- this means that the proteoglycans can carry a dense negative charge and will bind to a water molecule to form a hydrated gel that resist compressive forces
in what three ways are proteoglycan classified as
- according to their core protein
- localisation
- GAG composition
ecm mineral
- ecm can be mineralised
- calcium hydroxyapatite gives tough, hard mechanical properties
basement membrane role
- specialist ecm
- network of macromolecules
- cell attachment - separates epithelium and connective tissue
- gives cell signal to divide
- important in filtration in kidney
how do cells interact with the ecm
- cells can interact with the ecm through specialised membrane bound receptors (integrins)
- specific dimer pairing determines ligand binding
- mediates cellular effects
- bidirectional signalling molecules
how do cells modify the ecm
- cell can modify the ecm
- such as proteolytic enzymes - degrade the ecm
- release/activates growth factors
- altered expression in wound healing
wound healing process
- matrix forms structure for skin
- when wounded signalling changes
- fibrin acts as a signal to repair skin
- matrix changes
- granulation tissue forms to heal
- structure of skin formed
integrins in cancer
- ecm and integrin expression is changed in cancer
- integrin signalling influences cell growth, cell migration and anoikis
- targeting ecm and integrins in anti cancer therapy and imaging
ecm mechanics
- ecm can exist with different stiffness and elasticity
- dependent on composition
- affects cell behaviour
- integrins can acts as mechanosensors
- stiffness changes in disease
in order for new tissue to replace damaged tissue
- need to know molecules, mechanics of tissue, soluble signals