2. Extracellular matrix Flashcards by Caroline Mejlsted

What is the extracellular matrix?

The non-cellular components present within any tissue or organ
It provides essential physical scaffolding for the cellular components and initiates important biochemical and biomechanical cues that are essential for tissue morphogenesis

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How is the ECM important for mechanical support?

Gives the cells a substrate that they may migrate on

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What is the function of integrins?

Mediates cell adhesion to the ECM
It is involved in cell migration through the ECM

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Name 4 parameters of ECM

Stiffness
Fibre orientation
Ligand presentation
Dimensionality

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What are the fundamental components of the ECM?

Water
Polysaccharides
Proteins

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What are the two main classes of macromolecules in the ECM?

Fibrous proteins
Proteoglycans

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Describe proteoglycans

Proteoglycans consist of a protein core with carbohydrate chains linked to it
The carbohydrate chains are glycosaminoglycans (GAG) that are linked to the core protein with covalent bonds

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Where are proteoglycans found?

Proteoglycans fill most of the extracellular interstitial space in the tissue, in a form of hydrate hydrogel

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What are the main fibrous proteins in the ECM?

Collagen
Elastin
Fibronectin
Laminin

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What is the most abundant fibrous protein in the ECM?

Collagen
It constitues up to 30% of the total protein mass

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What is the function of collagen in the ECM?

Provide tensile support
Support chemotaxis
Regulate cell adhesion
Support migration
Direct tissue development

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Which cells primarily synthesize collagen?

Fibroblasts, a type of connective tissue cell
The fibroblasts may alter the configuration of the collagen, by arranging it in sheets or cables

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What type of collagen is more prevalent in mammals?

Collagen type 1

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How is collagen different between species?

Collagen is very conserved between species, which makes both allogenic and xenogenic sources of collagen effective as biological scaffolds
They have low antigenic potential

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Where is collagen type IV found?

In the basement membrane of all vascular structures

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Which type of collagen is found in the basement membrane of all vascular structures?

Collagen type IV

What is the function of collagen type VII?

It is the principal component of anchoring fibrils of keratinocytes to the underlying basement membrane in the epidermis

What is the function of collagen type VI?

It functions as a connector of functional proteins and glycosaminoglycans to larger structural proteins, such as collagen type 1, helping to provide a gel-like consistency of the ECM

What is the function of collagen type III?

It is found in selected submucosal ECM, where non-ridig structure is demanded for appropriate function

Which fibrous protein is associated with elastin?

Collagen

Which fibrous protein is associated with collagen?

Elastin

What is elastin?

A major fibre of the ECM that provides recoil to tissues that undergo repeated stretch
Elastin = elastic = stretchy

What is fibronectin?

It is important in organisation of the interstitial ECM and in cell attachment (by binding ECM to cell receptors)
It may be stretched greatly - several times over its resting length - due to cellular traction forces
Stretching of fibronectin exposes integrin-binding sites, which makes fibronectin an extracellular mechano-regulator
It is also important in cell migration during development.
It has many ligands for adhesion of many cell types, which makes it suitable for tissue repair scaffolds.
It is used as a coating protein on synthetic scaffold materials to promote host biocompatibility

What may synthetic scaffold materials be coated with to promot host biocompatibility?

Fibronectin

Where is laminin found?

In the ECM, especially within the basement membrane (basal lamina)

What is the function of tenascin?

Promote fibroblast migration during wound healing

What does the ECM consist of in tissues that are compliant (hollow tissue that distends with increasing volume)?

Collagen type I and III Elastin Fibronectin = these form a relaxed network of fibers that are surrounded and embedded into a hydrogel of proteoglycans containing glycosaminoglycan chains

Describe the senescent fibroblast

They are growth-arrested and resistant to apoptotic cues They express high levels of fibronectin, fibroblast metalloproteinase, growth factors, plasminogen activator inhibitor and mitochondrial-related ROS Chronic inflammation due to ROS and MMP destroys the integrity of elastin. Collagen fibers are crosslinked by glycosylation. This both gives stiffer tissues which are mechanically weaker, less elastic and more rigid.

Describe the role of the ECM in acute wound healing

Wounds lead to vascular damage and formation of a fibrin clot, which stimulates monocyte infiltration to the damaged ECM. Monocytes are differentiated to macrophages by ECM-degradation products and cytokines. Macrophages secrete growth factors, matrix metalloproteinases and cytokines, that promote angiogenesis and stimulate fibroblast migration and proliferation, to rebuild the ECM. The fibroblasts synthesize ECM proteins. Increased mechanical stress may differentiate the fibroblasts.

Explain the role of the ECM in tumours

ECM deposition and remodelling by fibroblasts make the tumours more stiff The pro-inflammatory environment activates fibroblasts to differentiate to myofibroblasts, which promotes tissue desmoplasia (growth of fibrous or connective tissue) Growth factors secreted by the myofibroblasts act on new collagen and elastin fibers, so they are reoriented and crosslinked, which generates more rigid fibrils

What may degrade ECM components?

Matrix metalloproteinase (MMP)

Name three types of cell-contacts that are based on integrins

Hemidesmosome Focal contacts Fibrillar contacts

What are hemidesmosomes?

Intracellular protein plaques in epithelial tissue that connects the basement membrane to cytoskeletal intermediate filaments through integrins

What are focal contacts and fibrillar contacts?

Specialised adhesion complexes Involved in mechanical linkage of ECM to the actin cytoskeleon

What are tight junctions?

They seal together neighboring cells in an epithelial sheet to prevent leakage of molecules between them. They form an impenetrable barrier by effectively fusing adjacent cell membranes together, so that no molecules can pass. The seal gives the tissue its barrier function (=think of the BBB, where tight junctions between BECs makes it impenetrable to large molecules)

What are adherence junctions?

Adherence bundles join an actin bundle in one cell to a similar bundle in a neighboring cell. A sort of back-up for tigh junctions, that allow a connection to the actin cytoskeletin that can be used to regulate the permeability of the tissue and provide mechanical strength

Whar are desmosome junctions?

Spot weld that anchors the tough intermediate filaments in one cell to those in a neighbour. Provides mechanical strength by anchoring cell-cell junctions to intermedaite filaments that are connected to the basement membrane through hemidesmosomes