Cell matrix signal Flashcards
extracellular matrix surround cells
chondrocytes - mesenchymal cell
cells sitting on matrix
epithelial, lining tube, skin
matrix
insoluble, amalgam of protein + proteoglycan = bed around cell
can be cell signalling molecules as well
dermis
below epithelial in skin
matrix function
for strength - tensile and compress - when pulled or pressed - returns back to original form
roles of matrix
integrate cells into tissue and limits it by setting boundaries
signal info to cells about surroundings
skin - dermis
loose connective tissue laid with many fibres
skin - dense connective tissue
laid - more defined regularly packed sheets
basement membrane
basal lamina between blood vessel, muscle, epithelium
basement membrane signalling function
migration - during development/ healing
cell survival and differentiation
basement membrane physical function
tissue border
strengthens
filter effect
basement membrane in ECM
structural protein
proteoglycan
cell adhesive protein
tensile strength by collagen
around 7 forms - act as fibrils/associated to fibrils or sheet
tensile strength characteristic
major structural protein and most abundant protein in body
collagen sequence
repeat of Gly-XY sequence 300-400 times
collagen helix
collagen sequence folds
LH helix than alpha
stable
trimeric collagen (TC)
3 helices wrap - RHS helix
RHS helix
right hand super helix
Gly-XY
XY - often lysine/ proline
modify to -OH form
fibrillar collagen
include collagen I, II, III
fibrillar collagen packing
loose connective - lots of collagen III
dense connective - more collagen 1 and 2
TC secreted
in ECM in regular array - places in off set array system
TC region
at high dense and less protein = bands in TEM and SEM
TEM/SEM
transmission/scanning e- micrograph
collagen formation
non-collagenous region (no GlyXY)
N and C terminal ends
collagenous repeat
at the centre
collagen formation
produced in ER and secreted
some XY
hydroxylated and other (selected hydroxylysines) - glycosylated
trimeric Shelix
3 chains (pro alpha chains) weaved at C-terminus to N which is then placed in secreted vacuole for secretion out of Golgi
shift base
used to form covalent linkage between trimeric collagen fibril
collagen formation on secretion
C and N terminal non-collagenous region is remove = mature collagen molecule - able to lay down in arrays into fibrils
cleaved by enzyme out of the cells
C and N terminal non-collagenous
prevent fibril forming inside cell
if removed inside cell - insoluble in Golgi and vacuole therefore kills the cell
collagen molecules characteristics
long half life
degraded/reformed at stress, healing, cell infiltration etc
mutation of enzyme used to cleave
can’t form fibrils
detect in collagen deposition therefore weakens it
MMP
matrix metalloproteinase
MMP function
released as they migrate through CT
regulate breakdown of collagenous matrix in its modelling
disease - ascorbic acid deficiency
scurvy - in absence collagen trimer and fibrils less stable - weaker
acid - cofactor for XY hydroxylase - for collagen crosslink
elastin
fibres formed of polymer elastic
monomeric tropoelastin
cross linkage
between elastin by hydroxy linkages
increase linkage over time
returning to original of elastin
lacks defined structure
highly HP = random coil which returns back
properties of elastin in tissues of
blood vessels
lungs
elastic cartilage
synthesis of elastin
during foetus and childhood
but very limited in later life = wrinkles
elastase
secreted by neutrophils
destroyed elastin replaced with collagen after fibres are broken down by inflammation
= fibrosis and scarring
proteoglycan
give compressive strength by water retention
core has highly charged sugar attached and attract H2O and Na+ = hydrated porous gel
hydrated porous gel
allow motion of nutrient and waste products about isolated cell
e.g. chondrocytes
sugar and GAG
repeated sequence of disaccharides (tetrasaccharide link) and GAG sequence
GAG sequence
glycosaminoglycan sequence
proteoglycan function - resistant to compression
alter charge density on pressure
charged chains repel and water gel like
proteoglycan function - highly charged
binding site for many molecules - GF(FGF) and cytokines (TGFb)
released on proteoglycan damage
proteoglycan function coreceptor
inducer for GF
cell adhesion molecule
fibronectin
laminin
fibronectin
in loose connective tissue
disulphide linked - dimer
6 domain in fibronectin
self association collagen binding cell binding heparin binding C-terminus
function of 6 domain in fibronectin
interact with different ECM molecules
C-terminus of 6 domain
small (RGD) and synergy region
RGD
Arg, Gly, Asp
bind to integrin - fibronectin act as link to surface and matrix
collagen binding and self-association - 6 domain
bind multiple fibronectin
heparin binding region
within heparin sulphate
cell binding of fibronectin via specific integrin receptor induces
remodelling of cytoskeleton
cell migration
proliferation
remodelling of cytoskeleton
signal cell to attach
cell migration
move - attach to surrounding - transport
proliferation of integrin receptor
in healing as example
laminin
a, b and y chain = trimer
laminin - G-domain
bind to receptor and integrin receptor and other receptors
sheet of laminin
trimer interacts in presence of Ca2+
self assemble mesh
centre go down and bind to receptor on cell surface
interacting with proteoglycans, collagen and cell receptors
basement membrane signals
migration, cell survival and differentiation
losing receptor in mesh
cell has tendency to die
integrin families matrix receptor
heterodimeric receptor - ab subunit separate
matrix receptor has transmembrane region
bind to linker and attach to part of cytoskeleton
specific integrin - function
bind to specific ECM components especially laminin and fibronectin
integrin
nucleation site for actin polymerisation = stable contact between contractile machinery and ECM
linkage from cytoskeleton - in cell and matrix out of cell
cell contract and movement
pull on actin filament and transfer force ECM
allow cell to generate traction
traction of cells for movement
lamellipodia
filopodia
lamellipodia (Lp)
push
large amounts of integrins
filopodia (Fp)
spike
extension
cell contraction and movement - migration
heals wounds
immune cell and metastasis (tumour)
moving forwards - in terms of Lp and Fp
Fp interacts with matrix and convert to Lp to move
focal adhesion
area of clustering
integrin binds to specific sequence on ECM
e.g. RGD receptor or more complex site
roles of focal adhesion
anchor cells to ECM
migration
signal from ECM
focal adhesion - actin filaments
comes in from cytosol and linker protein attach to integrin receptor - sits through membrane and binds to ECM
linker proteins on actin filments
vinculin
alpha-actinin
assembly of focal adhesion
has many fibre therefore huge cluster of integrins
hemidesmosomes
specific integrin bind laminin in BM to intermediate filaments (keratin) via plectin
BM
basement membrane
desmosomes
similar to hemidesmosomes
only has keratin filaments
difference between hemidesmosomes and desmosomes - function
act as interaction between keratin filaments between cells
while hemidesmosomes - intermediate filaments and BM
defect in molecule producing hemidesmosome/receptor/laminin
weak attraction from ECM to BM
therefore when force added on cell - pull away
= Epidermolysis bullosa
integrin clustering causes
with example
other signalling molecules bind to focal adhesion sites
concentrated at site
e.g. FAK - at high conc - function activate
ECM attached to integrins pathways
actin organisation
cell spreading
cell motility
survival proliferation
FAK
focal adhesion kinase
