Cell Biology- Extracellular Matrix

1)important for shape and organization of cells in organs
2)provides mechanical properties - tensile strength, compresive strength, elasticity
3)biochemical properties (signaling)

These 3 components lead to: development, protection, differentiation, migration, signaling, wound healing, diseases, tissue engineering

-something within or from which cells originates, develops, or takes form
-material in which cells is enclosed or embedded
ECM: complex network of polysaccharides and proteins secreted by cells and in which cells are embedded; mainly structural roles, but also signaling; all polysach. and proteins are made, secreted, organized, modified, degraded by cells.

1. collagen
2. fibronectin
3. elastin
4. laminin

Many types, very abundant, provides tensile strength (stiff), found in many tissues (esp. bone; tendons, ligaments, and skin)
Made up of a polypeptide chain, rich in gly (occurs every 3rd spot) and pro. Collagen monomer assembles with other monomers into triple helix- glycine shoved into middle.
Secreted protein, so folding in the ER (?)
has cleavage signal cleaved in ER
triple helix assemble happens in ER
Fiber-cross-linking outside the cell
endocytosis
fibers assembled outside the cell

1) can assemble into fibers or networks - non-fibrillar collagen
2) fibers- fibrillar collagen- triple helix for fibril- firbrils associate laterally and form a fiber.

1. collagen monomer made by cotranslational translation (?)- protein made on ribosome, docked on translocon. (ER)
2. hydroxylation- adding of OH groups on K and P residues (ER)
3. glycosylation
4. triple helix assembly- 3 come together by associating certain domains (all hydroxylated, glycosylated)
5. exocytosed - has propeptide, so called pro-collagen. If it didn't have propeptide, could assemble inside the cell. Cleave off the propeptide outside the cell so that they can assemble --> tropocollagen, assemble into fibrils.
6. each fibril asscoiated w other fibrils into fiber

Regulate cell adhesion, support cell migration, direct tissue development. If you have a plate covered in random collagen, put 3 blobs of cells on top- cells organize the collagen into long fibers that are between the regions of cells. The cells are able to crawl along the collagen fibers towards the other cells.

Single gene- has different domains- can mix + match to create different kinds.
Can interact w: Glycoprotein GAGS- matrix interactions or interaction w cell.
Collagen- matrix,
Integrin- cell,
GAGs- matrix,
glycoprotein- cell/ matrix.
Have a dimerization domain

Can unfold, has different function in unfolded. When unfolded, exposes new sites for fiber formation; enables stretching of ECM (elastic)

Give elastic properties to tissues. Stretchy rubber band, can be stretched many times. Important in blood vessels, lung, and skin. Molecules can be cross-linked via K residues. Have hydrophobic regions, so folded into random coils. Can be stretched out, cross-links keep their shape.

Structure of 3 different coils, that form a coiled-coil domain. beta and gamma chains interact wi laminins.
Alpha chain interacts w cells through integrins. Blob on gamma chain can interact w ECM. End of coiled cois can interact w cell through integrins. important for organization of ECM and cell attachment.
Found mostly in basal lamina- a thin sheet of ECM (epithelial cells)

Protein + glycosaminoglycan (GAG)
Differs from glycoprotein becuase its sugars are smaller, and may be branched verstion of sugars
determined by type, #, and arrangement of GAGs.
Negatively charged- can form a hydrogel by assocating w water (lots of space, very large)
-bind other ECM or signaling molecules
-involved in cell adhesion, migration, proliferation
-resist compressive forces
-large, contain a lot of water; can shrink if water is removed; resist forces if something is pushing on it

Long, linerar, highly negatively charged repreating disaccharide (>10 sugars), 1 of which is an amino sugar. Sugars are the GAGs. O-linked sugars added in Golgi, synthesized on protein w different enzymes.

Example of proteoglycan. resists compression in cartilage. Attached ot it is a GAG (that doesn't come attached to a protein. exception bcos all other GAGs have proteins). Linker proteins- can associate w other proteoglycan called aggrecan- constists of protein and GAGs (GAGs- keratin sulfate and chondroitin sulfate),
Can prevent a tissue from being destroyed when compressed.

Cells effect the ECM and the ECM effects cells. By making, modifying, rearranging. 1 experiment: set up slide w/ 1 half nothing and 1 half ECM on one side and the other. Cells act very differently on the ECM side than on the nothing side. Cell differentiation: mesenchymal cells can differentiate to many different cells. ECM plays a role in this. Experiment: 3 stem cell populations put in or on a matrix that has different elasticity (generated using polyacrylimide). Lowest stiffness: neuron.middle: muscle. stiffest: bone.