Lecture 21 - Cell adhesion and the ECM

Question 1

What is the ECM and what are its constituents?

Answer 1

In space between cells a special environment exists which causes cells of the same tissue to adhere together.

Cells secrete a complex set of proteins called the extracellular matrix. These ECMs consisit of cell - matrix interactions, cell - cell interactions, and linkages to the cytoskeleton.

Question 2

What are some locations to see lots of ECM?

Answer 2

Covering of teeth.

inside the eye

outside of tendons

Question 3

What is the function of the ECM?

Answer 3

Framework to support cells; it can support stresses of tension and compression

Communicates with cells to carry out specific functions

Defines the shapes of cells

Reservoir of growth factors and signaling molecules

critical for embryonic development. (ECM defines where cells migrate during embryonic development)

Regulates cell migration

Important in repair of wounded tissue (assists in cell migration to wound location)

Question 4

What are some defects that can arise in the ECM?

Answer 4

Defects in ECM leads to developmental malformation.

Remodelling of ECM by tumour cells in metastasis

Question 5

What does the cell-matrix interface contain?

Answer 5

Cell-cell adhesions

Glycosaminoglycans

Proteoglycans (proteins with large carbohydrates contained)

matrix proteoglycan

Multiadhesive proteins (binds cells to collagen fibers)

ECMs are highly dynamic and constantly being produced and destroyed.

Question 6

What are the 3 classes of macromolecules?

Answer 6

Fibrillar glycoproteins

Adhesive glycoproteins

Matrix proteoglycans and glycosaminoglycans

Question 7

What are basal lamina?

Answer 7

Specialised ECM that underlie epithelial cell sheets and surround muscle cells.

Question 8

Is the ECM the same for every layer?

Answer 8

No, ECM composed of basal lamina is different from connective tissue.

Question 9

What cells produce the ECM components?

Answer 9

Fibroblasts produce ECM structures.

Question 10

What are the basic characteristics of collagen?

Answer 10

Collagen is the main fibrillar component of ECM.

Bundles of collagen run at right angles to one another forming sheets.

Collagen is produced by fibroblasts.

Collagen can assemble into supramolecular aggreggates.

family of 18 proteins found in cartilage, cornea, bone, and skin.

1000 amino acids is the usual size of one helix.

arranged as a helix with 3 amino acids per turn

Gly-X-Y; X is typically proline and Y is often hydroxyproline.

Question 11

What are the characteristics of the supramolecular structure of collagen?

Answer 11

3 collagen polypeptides are wound around each other to form a triple-stranded helix.

Helical conformation is stabilised by proline.

glycine fits into the crowded interior allowing the helices to pack tightly into the triple helix.

Question 12

How is collagen synthesized?

Answer 12

1) Pro-alpha chain is produced by the ER.
2) Some prolines and lysines are hydroxylated.
3) Some of the hydroxylysines are glycosylated.
4) Self-assembly of three pro-alpha chains.
5) The three helices form a triple helix procollagen molecule.
6) Procollagen is secreted.
7) Outside of the cell the collagen fiber propeptides are cleaved (extensions of procollagen)
8) Procollagens self-assemble to form collagen fibrils.
9) Collagen fibrils form a collagen fiber.
* Vitamin C is essential for this process to occur.

Question 13

What is the result of a lack of collagenase?

Answer 13

Lack of collagenase that converts procollagen to collagen results in no collagen fibrils. This results in hyperextensible skin.

Question 14

How are collagen molecules linked together?

Answer 14

Via intermolecular cross-links between modified lysine side chains.

Question 15

Why is it that not all structures containing collagen have the same structural properties?

Answer 15

Organisation varies in different tissue and is very important for the integrity of the structures.

Question 16

What is the consequence of mutations in collagen genes?

Answer 16

Mutation in collagen genes are often lethal or result in severe diseases.

*Collagen genes are usually dominant

Question 17

What is the function of laminin and fibronectin in cells?

Answer 17

Fibronectin in connective tissue and laminin in basement membrane forms a direct contact between ECM and cells via cell surface receptors (integrins).

Question 18

How do cells maintain tension in their contact with the ECM?

Answer 18

Integrins allow a direct contact between the ECM and the cytoskeleton of the cell which is a more rigid structure than the cell membrane.

Question 19

How does integrin attach to laminin/fibronectin?

Answer 19

Integrin forms a receptor for fibronectin and laminin.

Question 20

What is the structure of fibronectin like?

Answer 20

Fibronectin is a dimeric protein joined together by a disulfide bond.

It contains multiple domains; 2 heparin binding domains, 2 cell binding domains, some collagen binding domains, and modules.

They can bind to collagen proteoglycan and cell surface receptors

Question 21

How does fibronectin bind to integrin in the plasma membrane?

Answer 21

Cell-binding module contains RGD sequence which is bound directly by integrin molecules in plasma membrane. Mutation in any of the residues results in an inability to bind integrin.

Question 22

What is the synergy sequence?

Answer 22

Synergy sequence is found on the other side of the fibronectin protein and doesn’t directly interact with integrin but is still important in the interaction.

Actin and fibronectin interact strongly together near cell surface.