ECM composition and function

Question 1

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What are the main functions of the extracellular matrix (ECM)?

Answer 1

1. Support and strength: Found in structures like the basal lamina, bone, and cartilage.
2. Cellular communication: Mediated by hormones, growth factors, and cytokines.
3. Regulating cell migration, polarity and shape: Important in embryonic development, angiogenesis, wound repair, and tumour development

Question 2

What is the basal lamina, and what is its composition?

Answer 2

A thin layer of ECM produced by cells above and below it.

Composed of laminin, type IV and XVIII collagen, nidogen, perlecan, and fibronectin.

Essential for maintaining epithelial tissues and is evolutionarily conserved

Question 3

What is unique about connective tissue compared to other tissues?

Answer 3

Reduced cellular content with rare cell-cell contact

ECM is the main stress-bearing component, forming an indirect means of cell-cell contact

Question 4

How much of the human body is made up of the ECM?

Answer 4

The adult human body contains approx 37 trillion cells with the rest of the body consisting of ECM

Question 5

What are the two categories of cells found in connective tissue?

Answer 5

1. indigenous cells: Primitive mesenchymal cells, fibroblasts, adipocytes, mast cells, chondrocytes, and osteoblasts
2. Immigrant cells: immune cells that migrate into connective tissue

Question 6

What are the 3 main components of connective tissue ECM?

Answer 6

1. High-MW, highly charged polysaccharides (GAGs/proteoglycans)
2. Fibrous proteins (e.g., collagen).
3. Glycoproteins (e.g., elastins, fibronectins).

Question 7

What specialised forms can ECM take?

Answer 7

ECM can become calcified (e.g., bone, teeth) or transparent (e.g., cornea)

Question 8

What are glycosaminoglycans (GAGs), and what is their function?

Answer 8

GAGs are the most anionic molecules in animals, consisting of repeating sulphated disaccharide units.

They bind water and are often linked to proteins to form proteoglycans (PGs).

Question 9

Name examples of GAGs

Answer 9

Heparin sulphate, ketarin sulphate, dermatan sulphate, chondroitin sulphate, and hylauronan.

Question 10

What is the structure of collagen?

Answer 10

• Long, stiff, triple-stranded helical structure
• Composed of three polypeptides (a chains rich in proline and glycine) that form a coil
• Provides tensile strength to tissues

Question 11

How is collagen classified into different types?

Answer 11

Collagen types are based on different a chain combinations
Examples: Type II and IX (cartilage), Type XVIII (basal lamina)

Question 12

What prevents collagen aggregation inside cells?

Answer 12

Procollagen, a precursor form of collagen, prevents premature aggregation.

Question 13

What is the role of elastins in ECM?

Answer 13

Provide elasticity to connective tissues
Dominant in arteries and help tissues withstand stretching

Question 14

What are fibronectins, and what is their function?

Answer 14

Glycoproteins that bind matrix and cell membrane proteins.
They organise the ECM and provide a link between cells and the ECM.

Question 15

What receptors do cells use to interact with the ECM?

Answer 15

Integrins, which bind ECM components and anchor cells to structures like the basal lamina.

Question 16

What is the structure of integrins?

Answer 16

Composed of α and β chains with a large N-terminal domain and a short intracellular domain.

The intracellular domain binds adapter proteins like talin.

Question 17

How do integrins strengthen cell-ECM contact?

Answer 17

By linking the ECM to the cytoskeleton via adaptor proteins, enabling the application of mechanical force.

Question 18

Why do integrins exist in an inactive conformation?

Answer 18

To allow cells to migrate through the ECM.

Integrins are activated as needed to form and break contacts during migration.

Question 19

What is the role of focal adhesion kinase (FAK) in integrin-mediated signalling?

Answer 19

FAK recruitment leads to altered gene expression, such as regulating ECM homeostasis

Question 20

How does the ECM facilitate cellular communication?

Answer 20

By interacting with cell surface receptors (e.g., integrins) to mediate intracellular signalling and influence gene expression.

Question 21

How do integrins enable cell migration?

Answer 21

By forming transient attachments to the ECM, allowing cells to “pull” themselves forward and detach when needed.

Question 22

What is the primary role of the ECM in connective tissues?

Answer 22

To provide structural integrity, facilitate cell communication, and support force transmission.

Question 23

What components make up proteoglycans (PGs)?

Answer 23

GAGs covalently attached to a core protein, which can be simple or complex and may self-aggregate

Question 24

How are glycoproteins distinct from collagen?

Answer 24

Glycoproteins like elastins and fibronectins are not part of the collagen family and have unique structural and functional roles.

Question 25

What is the significance of the ECM in embryonic development?

Answer 25

It guides cell migration, polarity, and shape, which are critical for tissue and organ formation

Question 26

How does the ECM contribute to angiogenesis?

Answer 26

By providing structural cues and mediating signalling pathways necessary for new vessel formation

Question 27

What role does the ECM play in wound repair?

Answer 27

It supports cell migration and regulates growth factors to facilitate tissue regeneration.

Question 28

How does the ECM influence tumour development?

Answer 28

By modulating cell adhesion, migration, and signalling pathways involved in cancer progression

Question 29

What is the significance of ECM calcification?

Answer 29

Calcification strengthens tissues like bone and teeth but is regulated to prevent pathological conditions.

Question 30

Why is the ECM considered essential for tissue strength and resilience?

Answer 30

Its fibrous proteins, GAGs, and glycoproteins provide structural support and allow tissues to withstand mechanical stress