Extracellular Matrix

From Cells to Tissue: Extracellular Matrix (ECM)

Reading List

  • Textbooks:

    • Molecular Cell Biology (Eighth Edition) by Lodish/Berk/Kaiser/Krieger/Bretscher/Ploeg/Garand

    • Relevant Part: Integrating Cells into Tissues (pages 921-975)

    • Molecular Biology of the Cell (Sixth Edition) by Alberts/Johnson/Lewis/Morgan/Raff/Roberts/Walter

    • Relevant Chapter: Cell-Cell Junctions (pages 1035-1085)

The Need for Cell Adhesion

  • Overview:

    • Some organisms are unicellular, leading to no permanent cell connections.

    • Unicellular organisms may adhere to surfaces or food sources.

    • Bacteria can exist in two forms:

    • Planktonic: Free in solution

    • Sessile: Attached to a surface or within a biofilm (initial attachment via pili, a virulence factor).

Transition to Multicellularity

  • Challenges faced during the transition from unicellular to multicellular forms:

    • Differentiation of cell roles and interactions

    • Mechanisms for cell adhesion, communication, and transport

    • Creation of specialized functional domains

Tissue Definition

  • A tissue consists of similar cells and extracellular matrix (ECM) from the same origin, fulfilling a specific function.

  • Organs form from the functional collaboration of multiple tissues.

Types of Tissues

  • Connective Tissues:

    • Characterized by low cell density and abundant ECM (e.g., bones, tendons)

    • Rare cell-cell contacts; ECM is load-bearing.

  • Epithelial Tissues:

    • Cells tightly bound into sheets (e.g., gut lining, skin epidermis).

    • Thin ECM structure known as basal lamina on one side.

What is the Extracellular Matrix?

  • Definition:

    • Material produced by cells and secreted into the surrounding medium; typically non-cellular portion of animal tissue.

    • Other organisms like plants and fungi produce their own form of ECM (cell walls); arthropods produce chitin.

    • Key Biopolymers: Chitin and cellulose are the most abundant.

Functions of ECM

  • Roles include:

    • Mechanical support: Provides tensile and compressive strength.

    • Protection: Buffers extracellular changes; retains water.

    • Organization: Influences cell behavior through growth factor binding and interaction with receptors.

Variations in ECM Classes

  • Different tissues exhibit variations in the composition of ECM macromolecules, leading to a diversity of mechanical properties.

Main Macromolecular Components of ECM

  • Glycosaminoglycans (GAGs):

    • Acidic polysaccharide derivatives, often forming proteoglycans.

  • Fibrous Proteins:

    • Includes collagen family members.

  • Non-Collagen Glycoproteins:

    • Example: Fibronectin and laminin.

  • Others:

    • Example: Elastin.

Glycosaminoglycans (GAGs)

  • Characteristics:

    • Unbranched polymers made of repeated disaccharide derivatives (including amino sugars).

    • Composed of components such as:

    • Galactose, Galactosamine, and other variants.

  • Properties:

    • Acidic and negatively charged; attract positive ions (e.g., Na+), promoting water retention and gel formation.

    • Comprise 10% of ECM mass, but 90% of volume; confer compressive strength.

Types of GAGs

  • Hyaluronan:

    • Large, non-sulfated GAG; holds open spaces in ECM for cell migration.

  • Others Include:

    • Chondroitin, Heparan, Dermatan, and Keratan sulfate variants.

Proteoglycans

  • Definition:

    • A serine-rich protein linked with GAGs; formed by assembling a specific tetrasaccharide on a serine side chain.

Aggrecan

  • A common proteoglycan, with its core protein linked to multiple GAG chains and associated with hyaluronan, forming large aggregates.

Silicon's Role in Cell Growth

  • Heparan sulfate binding influences cell growth and inflammatory responses.

Fibrous Proteins

  • Collagen:

    • Consists of three α-chains forming a triple helix, providing tensile strength.

    • Collagen chains contain repeating GXY sequences (G = Glycine, X and Y = commonly proline and hydroxyproline).

  • Elastin:

    • Provides elasticity to ECM, characterized by hydrophobic and proline-rich sequences.

Collagen Synthesis

  • Synthesis occurs in the rough endoplasmic reticulum (RER).

  • Procollagen is secreted, followed by cleavage of terminal propeptides and modifications like hydroxylation and glycosylation.

Collagen Maturation

  • Self-assembly into fibrils stable for extensive periods (up to 10 years).

  • Cross-linking occurs via oxidative deamination reactions.

Importance of Vitamin C

  • Required cofactor for proline hydroxylase enzyme; absence leads to scurvy due to weakened collagen tissues.

  • Historical perspective: James Lind's findings on citrus fruits curing scurvy.

Types of Collagen

  • Type I: Common in skin, bones, tendons.

  • Type II: Found in cartilage.

  • Type IV & VII: Form mesh structures (basal lamina).

The Basal Lamina

  • Functions:

    • Structural integrity, organization of cells, conflict barriers, and migration pathways.

  • Composition: GAGs (e.g., heparan sulfate), laminin, collagen, and nidogen.

2. The Evolution and Necessity of Cell Adhesion

  • Unicellular Dynamics:

    • Exist in planktonic (free-floating) or sessile (attached) states.

    • Biofilms: Complex communities of microbes where bacteria adhere to surfaces via pili (specialized appendages) and secrete an extracellular polymeric substance (EPS).

  • Transition to Multicellularity:

    • Requires mechanisms for cell-cell recognition and stable adhesion.

    • Development of specialized junctions: Adherens junctions and desmosomes for mechanical strength, and tight junctions for permeability barriers.

    • Tissue Architecture: Defined by the spatial arrangement of cells and the surrounding Extracellular Matrix (ECM).

3. Classification of Animal Tissues

  • Connective Tissue (e.g., bone, cartilage, tendon, dermis):

    • High ECM to cell ratio; the matrix is the primary load-bearing element.

    • Cells (mostly fibroblasts, osteoblasts, or chondrocytes) are sparsely distributed.

  • Epithelial Tissue (e.g., gut lining, skin epidermis):

    • High cell density with minimal ECM between cells.

    • Cells are attached to a specialized thin sheet of ECM called the Basal Lamina.

    • Mechanical stresses are transmitted from cell to cell via cytoskeletal filaments anchored to adhesion junctions.

4. The Extracellular Matrix (ECM): Structure and Function

  • Definition: A complex network of proteins and polysaccharides secreted locally by cells into the extracellular space.

  • Core Functions:

    • Mechanical Support: Resistance to tension (collagen) and compression (GAGs).

    • Hydration: GAGs attract water, maintaining tissue turgor.

    • Biological Signaling: Acts as a reservoir for growth factors and cytokines, regulating cell proliferation, differentiation, and migration.

    • Tissue Scaffolding: Provides a substrate for cell migration during development and wound healing.

5. Molecular Components of the ECM

5.1 Glycosaminoglycans (GAGs)

  • Chemical Structure: Unbranched chains of repeating disaccharides (sugarA−sugarBsugar A - sugar B).

  • Charge Density: Highly negatively charged due to sulfate and carboxyl groups, attracting cations like Na+Na^+ and creating high osmotic pressure (inducing water influx).

  • Major Types:

    • Hyaluronan: The simplest GAG; not sulfated; synthesized at the plasma membrane rather than the Golgi. Important for providing "space" during morphogenesis.

    • Sulfated GAGs: Chondroitin sulfate, Dermatan sulfate, Heparan sulfate, and Keratan sulfate.

  • Proteoglycans: Formed when GAGs (except hyaluronan) are covalently linked to a serine-rich core protein.

    • Aggrecan: A massive proteoglycan prevalent in cartilage that aggregates with hyaluronan to resist heavy compressive forces.

5.2 Fibrous Proteins

  • Collagen: The most abundant protein in the human body.

    • Molecular Structure: A triple helix formed by three α\alpha-chains. Recurring sequence: Gly−X−YGly-X-Y, where GlyGly is Glycine (small enough to fit in the helix center), and X,YX, Y are often Proline and Hydroxyproline.

    • Synthesis: Occurs in the Rough ER/Golgi as procollagen; terminal propeptides prevent premature intracellular assembly.

    • Extracellular Assembly: Propeptides are cleaved by procollagen peptidases, allowing the formation of collagen fibrils and fibers.

    • Vitamin C (Ascorbate): Essential cofactor for prolyl/lysyl hydroxylase enzymes; deficiency prevents hydroxyproline formation, leading to unstable helices and scurvy.

  • Elastin: Imparts elasticity and resilience; characterized by hydrophobic segments and cross-linking that allow the protein to recoil after stretching.

5.3 Adhesive Glycoproteins

  • Fibronectin: Helps cells attach to the ECM by binding to both collagen and integrins (cell-surface receptors).

  • Laminin: A primary component of the basal lamina; vital for cell polarity and structural organization.

6. The Basal Lamina (Basement Membrane)

  • Composition: Primarily Type IV collagen (forming a 2D mesh), laminin, perlecan (proteoglycan), and nidogen.

  • Specialized Roles:

    • Filtration: In the kidney glomerulus, it acts as a molecular sieve.

    • Polarity: Defines the apical and basal domains of epithelial cells.

    • Barriers: Prevents the migration of epithelial cells into connective tissue (crucial in cancer pathology where breach leads to metastasis).

7. Summary of ECM Diversity

  • Bone: Calcified matrix dominated by Type I collagen.

  • Cornea: Highly ordered collagen arrangement for transparency.

  • Tendon: Parallel bundles of collagen for maximum tensile strength along one axis.

  • Cartilage: High Aggrecan/Hyaluronan content for shock absorption.