Cell and Mollecular Biology - Extracellular Martix and Cell Adhesion

What is the ECM?

The extracellular matrix is the network of molecules outside cells that provides structural support, helps organize tissues, and sends signals that influence cell attachment, movement, survival, and behavior. It includes proteins and carbohydrate-rich molecules.

Proteoglycans vs. typical glycoproteins

Proteoglycans have a core protein with many long glycosaminoglycan (GAG) chains attached; carbohydrate makes up a large proportion of the molecule. Typical glycoproteins have shorter, branched carbohydrate chains attached to a protein, and the protein portion is usually more prominent.

What are GAGs, and what do they do?

Glycosaminoglycans are long, usually negatively charged repeating sugar chains. They attract positively charged ions and water, forming hydrated gels that resist compression, fill space, and help tissues retain water. Some GAGs are attached to core proteins in proteoglycans.

Fibronectin

An ECM glycoprotein that binds cells (often through integrins) and other ECM components. It helps connect cells to the matrix and supports cell adhesion and migration.

Collagen

A strong, rope-like fibrous protein that provides tensile strength and helps tissues resist pulling forces.

Laminin

A major basement-membrane protein that helps organize the basement membrane and supports cell attachment through interactions with cell-surface receptors such as integrins.

How ECM composition affects tissue mechanics

Different mixes of collagen, hydrated GAGs/proteoglycans, and adhesive proteins give tissues different properties. Collagen resists tension; hydrated GAG-rich material resists compression; adhesive proteins organize connections between cells and the matrix.

What distinguishes a proteoglycan from a typical glycoprotein?

A proteoglycan has a core protein heavily decorated with long GAG chains; a typical glycoprotein generally has shorter, branched carbohydrate chains.

How do GAGs contribute to ECM properties?

Their negative charges attract water, creating a hydrated gel that cushions tissue, resists compression, and fills the space between cells.

What do fibronectin, collagen, and laminin do?

Fibronectin helps link cells to matrix components; collagen provides tensile strength; laminin organizes basement membranes and helps cells attach to them.

How do integrins connect outside to inside?

Integrins are transmembrane α/β heterodimers. Their extracellular portions bind ECM proteins; their intracellular tails connect indirectly to cytoskeletal filaments through adaptor proteins. This creates a physical and signaling link between the ECM and the cell interior.

Why are adaptor proteins needed?

Integrin tails generally do not bind actin or intermediate filaments directly in the way needed for a stable junction. Adaptor proteins connect the integrins to the appropriate cytoskeletal network and help organize signaling complexes.

Integrin vs. cadherin adhesion

• Integrins mainly mediate cell–ECM attachment.

• Cadherins mainly mediate calcium-dependent cell–cell adhesion by binding cadherins on neighboring cells and linking to the cytoskeleton through junction proteins.

Tight junction

Forms a seal between neighboring epithelial cells, controlling what can pass between them (paracellular permeability). It is linked to actin.

Adherens junction

Provides cell–cell adhesion through cadherins linked to actin. It helps tissues maintain shape and coordinate changes in cell shape.

Desmosome

A strong cell–cell anchoring junction. Desmosomal cadherins connect neighboring cells, and the junction links to intermediate filaments, helping tissues withstand stretching and mechanical stress.

Hemidesmosome

Anchors a cell to the basement membrane/ECM rather than to another cell. It uses integrins and connects to intermediate filaments.

Gap junction

A channel between neighboring cells made from connexon assemblies. It permits selected small molecules and ions to pass directly from one cell's cytoplasm to another's.

Connexon

A channel-forming unit made of connexin proteins. Connexons in adjacent cells align to create a gap-junction channel.

Why are desmosomes important under mechanical stress?

Their links to tough intermediate filaments distribute pulling forces across cells and tissues, reducing the chance that cells will separate.

Desmosome vs. hemidesmosome: key difference

A desmosome connects cell to cell; a hemidesmosome connects a cell to the basement membrane/ECM. Desmosomes use cadherins; hemidesmosomes use integrins.

Gap junction vs. tight junction

Gap junctions allow direct communication through channels between cells. Tight junctions form a barrier that restricts movement between cells.

Why might integrin disruption affect basement-membrane attachment more than cell–cell adhesion?

Integrins are major cell–ECM receptors, including in hemidesmosomes. Many cell–cell junctions instead rely on cadherins, so they may not be directly disrupted by loss of integrin function.