Lecture 40: The extracellular matrix Flashcards
Tuesday 21st January 2025
Is it true that eukaryotic cells exist in a tissue environment with other cells?
Yes
How do eukaryotic cells in a tissue environment interact with other cells?
- Via the extracellular matrix
- Via cell-cell junctions (next lecture)
Is it true that the ECM is a major product of the secretory pathway?
Yes
Why is the ECM important?
- Provides structure and scaffolding to tissues.
- Anchors the cytoskeleton of cells indirectly.
- Enables Cell communication, migration, and interaction
- Enables Tissue-specific composition
- Enables Survival, development, proliferation, and shape determination
- Different tissues have a different ECM composition
Explain how different tissues have a different ECM composition?
- Dense CT (bone, teeth, tendon): Thick ECM with mechanical roles.
- Loose CT (gut lining, skin, cornea): Thin ECM, relies more on cell-cell junctions.
What are the key functions of the ECM?
- Mechanical Support:
- Strength (collagen)
- Elasticity (elastin)
- Turgor (hydration from polysaccharides)
What is the biological influence of the ECM?
- Influences gene expression, signalling, behaviour
- Provides medium for migration
- Participates in development and repair
What are the 2 main categories that the ECM is composed of?
- Polysaccharides and proteins
What polysaccharides is the ECM composed of?
- Glycosaminoglycans (GAGs)
- Proteoglycans
Descibe Glycosaminoglycans (GAGs) (one of the polysaccharides that makes up the ECM)
- Long unbranched negatively charged disaccharide chains
- Hydrophilic → Attract Na+ and water, creating hydration & turgor
Give some examples of GAGs
- Hyaluronan (Hyaluronic Acid) – Creates turgor, resists compression
- Dermatan sulfate – Tissue development
- Heparan sulfate, Keratan sulfate
Describe Proteoglycans
- MAde up of Proteins + GAG chains
- Up to 95% carbohydrate by mass
- Synthesised via secretory pathway (ER → Golgi → exocytosis or membrane anchoring)
Give an example of and describe a Proteoglycan
- Syndecan
- Transmembrane proteoglycan
- Interacts with growth factors
- Participates in signalling via cytoplasmic and extracellular domains
What are the different types of proteins that can be found in the ECM?
- Fibrous Proteins, like collagen and elastin
- Glycoproteins, like Fibronectin
Describe the fibrous protein collagen
- Provides strength
- Makes up approximately 25% of the protein in the body
- 90% of the collagen in our body is type I
- Requires vitamin C for proper hydroxylation (proline/lysine → hydroxy forms)
Describe the fibrous protein elastin
- Provides elasticisty
- Hydrophobic, extensively cross-linked
- Prominent in arteries
Describe the glycoprotein fibronectin
- Is important in regenration and adhesion
- Dimeric, binds ECM molecules and integrins on cells
- Helps link cytoskeleton to ECM (via actin-talin-integrin-fibronectin-ECM chain)
- Enables ECM organisation through cellular tension
Collagen included in previous lecture
Collagen included in previous lecture
What is another name for the basal lamina?
- The basement membrane
-
Does the basal lamina lie beneath epithelial cells?
Yes
What does the basal lamina contain?
Laminin – cross-shaped glycoprotein
Type IV Collagen – forms mesh-like X-tetramers
Nidogen, Perlecan – additional support
What is the function of the basal lamina?
Allows mechanical anchoring, filtering, and signalling
What is ECM degradation needed for?
Cell division
Migration (e.g., leukocytes)
Tissue repair/remodelling
Which enzymes are involved in ECM degradation?
- Matrix Metalloproteinases (MMPs)
Serine proteases
Is ECM degradation tightly regulated?
yes
In many cancers, is fibronectin expression reduced?
Yes
What happens when cancer reduces fibronectin expression?
- Weakened cell-ECM adhesion.
Easier for cancer cells to detach from their original tissue.
Promotes invasion of surrounding tissues.
Facilitates metastasis (spread to other parts of the body).
- 👉 This weakening of ECM ties enables tumor cells to migrate, which is key for spreading (metastasis).
Are MMP’s overexpressed in someone who has cancer?
- Yes
- This promotes tumour invasion and neoangiogenesis
