Cellular adhesion and extracellular matrix

What is the ExtraCellular Matrix (ECM)?

A non cellular 3D structural network that support the cellular components to form tissues and organs

What are the main components of the ECM?

Cells, water, fibrous structural proteins, fibrous adhesive proteins, polysaccharides

What are fibroblasts?

Connective tissue workhorses

What do fibroblasts do?

Synthesize and secrete most of the macromolecules of the ECM

What is the shape of fibroblasts?

Spindle shaped, motile

What is the role of fibroblasts in wound healing?

Migrate to the wound to synthesize matrix to restore tissue

What can out of control fibroblast secretion cause?

Fibrosis (Lungs)

What are the functions of the ECM?

Provides support and anchorage for cells

regulates cell dynamic behaviour

provides mechanical support for tissues and organ architecture

place for active exchange of metabolites, ion and water

What cell behaviours does ECM regulate?

Cell polarity, cell differentiation, adhesion, migration

What tissue processes does ECM support?

Growth, regenerative and healing processes, determination and maintenance of structure

What is collagen?

A fibrous structural protein of the ECM

What are the properties of collagen?

Resist tension, stretchable

How common is collagen?

Most common ECM protein and most common protein in mammals (35%)

What is the structure of collagen?

Triple helix

What amino acid sequence repeats in collagen?

Gly-X-Y

Which amino acid occurs every third position in collagen?

Glycine

What is usually found in the X position of collagen?

Proline

What is usually found in the Y position of collagen?

Hydroxyproline or hydroxylysine

What stabilises collagen helices?

Hydroxyproline and hydroxylysine help stabilise the helix

Who are the principal producers of collagen fibres?

Fibroblasts

Which other cells secrete type IV collagen?

Epithelial and smooth muscle cells

What periodic pattern is seen in collagen fibrils under electron microscope?

Cross striations every 67 nm

Where is Type I collagen found?

Bone, skin, tendon

Where is Type II collagen found?

Cartilage

Where is Type III collagen found?

Reticulin, liver, lymphatics, blood vessels

Where is Type IV collagen found?

Basal lamina

What is the first step in collagen synthesis?

Gene for collagen is transcribed into mRNA

Where are pro-alpha chains synthesized?

By ribosomes

What sequence do pro-alpha chains contain?

Gly-X-Y

Where does preprocollagen form?

Rough endoplasmic reticulum (rER)

What modifications occur to preprocollagen in the rER?

Hydroxylation and glycosylation

What is procollagen?

Triple helix (superhelix) collagen molecule

Where is procollagen sent after rER?

Golgi apparatus into secretory vesicles

How is procollagen released from the cell?

Exocytosis

What happens to procollagen in the extracellular space?

Procollagen peptidases remove terminal propeptides

What does procollagen become after cleavage?

Tropocollagen

What is tropocollagen?

Functional collagen monomer

How are collagen fibrils formed?

Tropocollagen molecules self-assemble in a staggered arrangement

How are collagen fibres formed?

Many fibrils cross-link to form functional collagen fibres

What is elastin?

Elastic protein able to regain the original shape

Where is elastin found?

Blood vessels, skin, lungs

What are fibrous adhesive proteins of the ECM?

Fibronectin, fibrillin, laminin, tenascin, vitronectin, osteonectin

What is fibronectin?

Main adhesion protein of connective tissues

What is the structure of fibronectin?

Homodimer protein

What can fibronectin bind to?

Cell surface, other fibronectin proteins, collagen and GAGs

What is fibronectin responsible for?

Cell adhesion and cell migration

What is laminin?

Adhesion protein of basal lamina

What is the structure of laminin?

Heterotrimeric: α, β and γ chains

What does laminin link?

Cells and matrix

What can laminin bind to?

Cell surface receptors, integrins, type IV collagen, proteoglycans

What is laminin responsible for?

Glomerular filtration in the kidney

What are glycosaminoglycans (GAGs)?

Repeating units of disaccharides

What sugars are found in GAGs?

N-acetylglucosamine or N-acetylgalactosamine with glucuronic acid or iduronic acid

Why do GAGs attract water?

Sulphate groups are negatively charged and attract positive ions which trap water

What do polysaccharides in the ECM do?

Fill space between cells and create gel-like environment

What are proteoglycans made of?

Protein core with chains of sugars attached

What are proteoglycans responsible for?

Hydration and cell protection

Where are GAGs abundant?

Cartilage

What are the two types of cell adhesion?

Cell-cell adhesion and cell-matrix adhesion

Why are cell-cell interactions important?

Critical for development and function of multicellular organisms

What are transient cell-cell interactions?

Activation of immune cells and migration to injury site