Extracellular matrix Flashcards
*What is the extracellular matrix?
It is an intricate network of collagens, proteoglycans and adhesion proteins interacting with soluble growth and differentiation factors (interacting with growth factors).
*What are the two types of ECM?
Basement membrane
- Thin layers of ECM that form the supporting structure on which all epithelial and endothelial cells grow.
- Promotes differentiation (of cells)
- Induces polarity (charge)
Stromal or Connective tissue
- Derived primarily from mesoderm (germ layer)
- Takes stress of movement
- Maintains shape
- Structure and function depends on relative properties of constituent molecules
*Outline collagen types, characteristics and function within ECM.
There are 29 distinct types of collagens, and three groups:
- Fibrillar
- FACIT (fibril associated collagens with interrupted triple helices)
- Non fibrillar
their primary characteristics are:
- they all possess basic structure of three polypeptide chains wound round each other
- one glycine every third residue, the rest being rich in proline, hydroxyproline, lysine and hydroxylysine which form cross links with and between molecules.
- they all go through post-translational hydroxylation of specific proline and lysine residues. This means functional groups are modified. There is further glycosylation of some hydroxylysines (addition of a sugar molecule).
Collagens all have the ability to form highly organised supramolecular assemblies in the extracellular space.
*Outline proteoglycan types, characteristics and function within ECM.
Proteoglycans are a diverse family of molecules, composed of core proteins with one or more glycosaminoglycan (GAG) sidechains. 4 types of GAGs:
- Chondroitin sulphate
- Heparan sulphate
- Keratan sulphate
- Hyaluronan
Function of proteoglycans: Various biological processes outside cells. Two examples:
Aggrecan
- Found as huge multimolecular aggregates comprising numerous monomers non-covalently bound to hyaluronan.
Decorin
- Associated with fibrillar collagen, and it binds to type VI collagen.
- Exhibits an interesting interaction with TGF-beta. TGF-beta may be held in ECM by decorin to be used in times of damage for repair.
*Outline glycoprotein types, characteristics and function within ECM.
glycoprotein
- carbohydrate attached to a protein core
- many have distinct, functionally active domains that interact with cell surface receptors and other matrix molecules.
Adhesive glycoproteins
- fibronectin, vitronectin, laminin
- All possess distinct structural and functional sites
- many have a strong negative charge which are associated with mineralisation and Ca2+ binding.
*What are cell-matrix interactions?
Hint - 7
This is an interaction between cells and the ECM. they participate directly in:
- Promoting cell adhesion
- Migration
- Growth
- Differentiation
- Programmed cell death.
- Modulation of cytokine and growth factor activities.
- Direct activation of intracellular signalling.
Describe receptors to ECM molecules.
Integrins
- Glycoproteins that act both as adhesion molecules and in signalling pathways, transmitting signals both into and out of the cell.
- Aggregate (come together) to initiate focal adhesion formation, which are essentially holding points that form mechanical links with ECM
Membrane associated proteoglycans and GAGs also act as ligands for ECM molecules.
*What are growth factors and how do they interact with the ECM? How do they mutually benefit each other?
These are signaling proteins that stimulate cell growth, differentiation, survival, inflammation and tissue repair. Growth factors and cytokines interact with the ECM in a variety of ways which allow them to mutually affect each other
ECM can affect the local concentration and biological activity of growth factors by:
- Acting as a reservoir for growth factors (gathers them
- presenting them more efficiently to receptors
Alternatively, growth factors can affect ECM:
- TGF-beta can alter production of ECM molecules, inhibitors and receptors.
Some ECM effects involve cooperation with growth factors.
*How can the ECM affect implantation site?
Fibrosis around implant (thickening and scarring of tissue)
- in response to device implantation, fibroblasts are activated to a proliferative and fibrogenic state.
- fibrosis occurs due to excessive proliferation and ECM production
- continued ECM remodelling shifts from a complex matrix to collagen I rich matrix, causing further fibroblast activation
The result of this is implant encapsulation
*Define mechanotransduction and explain how it relates to the ECM.
Cells have the ability to receive mechanical stress from their environment, and respond by improving the capacity of tissue to accomodate for it, known as mechanotransduction.
Biomaterials must be matched to the functional and mechanical characteristics of ECM present in the specific tissue. As cells adhere to a material at multiple sites, they may be able to sense forces to which the device is subjected and produce ECM in response.
Stresses applied to a cell via the cytoskeleton influence ECM remodelling, with cell-cell contact extending this stress field. This means it is very important to match mechanical properties of a material to those of the tissue to be restored, and provide sites for normal cells to attach.
