ECM Flashcards
Definition of ECM
insoluble part of the substance surrounding the cell, complex network of proteins and carbs, fibrillar and non-fibrillar
Function of ECM
physical support, mechanical and physiochemical properties, influence growth adhesion and differentiation, development tissue function and organogenesis.
relationship between ECM and connective tissue
high proportion of ECM in connective tissue surrounding very few cells cells don’t touch, in comparison to epithelium in which the cells are very tightly packed. basal membrane separate epithelial from connective tissue
describe scurvy
lack of vitamin C essential for hydroxylation of proline and lysine which allow collagen fibres to form hydrogen bonds
What is caused by a lack of collagen
stretchy skin
describe marfan’s syndrome
mutation in fibrillin 1 - tall, elastic fibres: skeletal, ocular, and cardiovascular system, predisposed to aortic ruptures. differs depending on the mutation, many different mutations.
what caused osteogenesis imperfecta
type 1 collagen
describe Alport’s syndrome
Type iv collagen (a5) filtration issue and lack of kidney function, affects ears.
describe epidermolysis bullosa
Laminin 5 in all chains
what causes congenital muscular dystrophy
Laminin 2 a2
gene mutations affecting ECM catabolism
Hurler’s syndrome - L-a-iduronidase
mucopolysaccharidoses - inability to degrade GAGs
fibrotic disorders
liver fibrosis - cirrhosis
kidney fibrosis - diabetic nephropathy
lung fibrosis - silicosis
what is caused by excessive loss of ECM
osteoarthritis
ehler’s danlos syndrome - collagen cant hold without tensile strength
major components of ECM
Collagen elastin integrin multi - adhesive glycoproteins proteoglycans
collagen characteristics
fibrous
42 genes 27 types
composed of alpha polypeptides form fibrils
three polypeptided aggregate forming a triple helix rope like structure with the same or different alpha chains type II and III only one chain type
each third AA is glycine, so that it fits in structurally
fibrils line up in parallel and form fibres
Propeptides, non collagenous domains at C and N, removed when leave Golgi
joined by covalent bonds
vit C and Fe2+ hydroxylates lysine and proline allowing more hydrogen bonds to form adding to the strength.
lysine and hydroxylysine modified for covalent bonds
fibril associated collagens
type IV - network forming collagen
sheet like network
have propeptides, aggregate together.
collagen function
tensile strength, resistant to stretching, skin bone and cornea perpendicular - resist stretch in all directions, tendon parallel - tensile strength in one direction
elastin characteristics
elastin and microfibrils
globular monomers
mix of hydrophobic and alpha helical regions - alanine and lysine
lysine side chains - covalently cross linked
Elastin core and microfibrils (rich in fibrillin)
Allow tissues to stretch
elastin function
allow stretching. skin, blood vessels dilate, lungs inflate and deflate
integrin
transmembrane receptor - bind to ECM and cytoskeleton - proteoglycans are attached to cytoskeleton
bind to laminin
hyaluronan
(gag chain) - no core protein, cube each side same size as collagen fibre, synthesised at cell surface, unsulfated.
proteoglycan
decorin
associated with collagen, regulates the size of the fibres and makes sure that they are all regular. 1 gag chain, dermatan sulphate
proteoglycan
aggrecan
-100 gag chains, - cartilage. hyaline cartilage aggrecan bind to hyaluronan (Link protein), aggrecan v. negative with sulfate and carboxylate groups attract anions and so water - resistant to compression. in oesteoarthritus the aggrecan fragments cant retain as much water - inflammation, rubbing of bones and formation of new bones.
proteoglycan
how does gag chain link to proteoglycan
gag chain always bind to proteoglycan vua serine and a specific heterosaccharide.
biosynthesis of collagen
post translational modifications - procollagen is secreted from the cell in a vesicle, and the propeptides are cleaved
hydroxylation of lysine and proline, modifications of lysine and hydroxylysine for covalent bonds
assembly of collagen
alpha chains - protein synthesis
hydroxylation and glycosylation
triple helix form from three alpha chains - fibril
propeptides cleaved
fibril line in parallel, covalent and hydrogen bonds mean they bond and form collagen fibres
definition of basement membrane
Flexible, thin mat of ECM underlying epithelial sheets and tubes
function of basement membrane
Separates the connective tissue from the epithelial tissue
proteins in BM
large, multi-adhesive and multifunctional - due to the many domains
laminin
glycoprotein
3 chain, alpha beta gamma, alpha biggest bind integrin dystroglycan and perlecan, gamma self adhesive and nidrogen and beta self assembly
globular domains
cross shape
absence of alpha 2 chain leads to muscular dystrophy - hypotonia, weakness, deformaties of joints
fribronectin
V shaped - bind to collagen and cell receptors
glycoprotein
splicing makes variations
disulphide at c terminal
because it can interact with cells it regulates cell adhesion.
RGD - integrin recognise motif and so this is where they bind
make mechanical continuum with cytoskeleton (actin)
proteoglycans in BM
core protein with GAG chains
perlecan is the one in the basement membrane
collagen in BM
IV
till has propeptides - join together forming matrix
