Lecture 16 - From Cells to Tissues

Question 1

What is the role of the extracellular matrix?

Answer 1

Extracellular matrix houses the cells
Cells have important physical interaction with extracellular matrix via integrins, which are expressed in the cell membrane and form interactions with components of the ECM
Tissues are composed of cells and (often) extracellular matrix (ECM) - exceptions would be skin epidermis - no ECM.
ECM is composed of proteins and proteoglycans.
Connective tissues form the framework of the vertebrate body, but the amounts vary for different organs.
Physical properties of different tissues can vary from hard structures, such as bone, to transparent, such as the cornea.
The ECM is not just an inert scaffold to stabilise the physical structure of tissues - can shape cell behaviour and differentiation, guide cell division, provide niche for stem cells, provide growth factors and regulate how cell receives those growth factors
The ECM helps to define the cellular phenotype of cells residing within it.
The ECM acts as a storage compartment for cell signalling factors.

Question 2

Describe the role of collagens in ECM composition

Answer 2

Represent ~25% of the total mammalian proteins
Composed of homo- or hetero-trimers and form a triple helical structure.
They give tissues tensile strength.
Amino acid sequence consists of Gly-X-Y repeats.
X and Y often Proline, Hydroxyproline or Hydroxylysine
Vitamin C, essential cofactor
Very broad family of ECM proteins
Have very similar structures, essentially triple helices, but can be arranged in different ways to form different structures
Gly-X-Y amino acid structure = glycine every third residue
Vitamin C required for hydroxylation of proline and lysine residues
Amino acid chain forms alpha chains, collagen molecules then wrap into collagen fibrils, those fibrils then associate to form fibres

Question 3

What is osteogenesis imperfecta?

Answer 3

Very severe condition associated with fragility of the skeleton - bones can be fractured very easily by any slight trauma
Varies in severity
Caused by mutations in collagen genes
Mutations in a1(I) or a2(I) genes

Question 4

What is dermatosparaxis

Answer 4

an inherited disorder:
Dermatosparaxis causes fragile and loose skin with substantial bruising and bleeding.

Also causes hypermobility of the joints

Caused by mutations in the N-terminal propeptidase that removes the propeptides in type I and III collagen.

N-terminal propeptidase = The Metalloproteinase ADAMTS-2

Question 5

Describe the role of proteoglycans and GAGs in the composition of the ECM

Answer 5

Glycosaminoglycans (GAGs) are covalently attached to a core protein to form proteoglycans
Provide hydrated, space-filling functions and compressive strength (e.g. in cartilage).
Glycosaminoglycans (GAGs):

Four classes of GAGs, formed by polymerisarion of specific disaccharides and modification (e.g. sulphation):

Hyaluronan (HA)
Chondroitin Sulphate (CS)
Heparan Sulphate (HS)
Keratan Sulphate (KS)

Question 6

Describe the role of elastin in composition of the ECM

Answer 6

Provides elasticity to help regulate tissue function
Elastin gives tissue
elasticity, allows stretching

Elastin consists of
covalently linked monomers.
Elastin is the dominant ECM component of arteries at ~ 50%.

Also found in lungs, elastic ligaments.

Question 7

What is cutis laxa?

Answer 7

Rare inherited disorder of connective tissues.

Skin inelastic and hangs loosely caused by mutations in several genes that affect elastin formation and function. Hypermobility of the joints may also feature.

Question 8

Describe the role of fibronectin in composition of the ECM

Answer 8

Large glycoprotein, helps matrix organisation.

Homodimer has binding motifs for proteoglycans, cells and collagen.
Multiadhesive protein, can bind to lots of things because of its structure. Dimer - smaller structure than collagen
Domains labelled with different binding domains
RGD domain recognised by integrins

Question 9

How does the ECM regulate cell behaviour

Answer 9

Anchorage dependence and cell survival.
Most cells need to attach to the ECM to grow and proliferate and, in many cases, to survive.
This is known as anchorage dependence.
Mediated by integrins and the signals they generate.
ECM geometry and organisation can regulate cell function.

Question 10

What is the basal lamina?

Answer 10

basement membrane, separates the epidermis and dermis
Specialised ECM structure made up of different types of ECM components
Composed of entactin, perlecan, laminin, type IV collagen
Flattened structure very different to fibrillar collagen. Made of type IV collagen, provides backbone to flat sheet-like structure