Extracellular Matrix (ECM) and Cell Adhesion

Comprehensive vocabulary flashcards covering the components, structure, assembly, cell-matrix junctions, mechanical transduction, and signaling pathways of the Extracellular Matrix (ECM).

Extracellular Matrix (ECM)

The non-cellular material distributed throughout tissues composed of water and an intricate network of macromolecules that holds water, provides structural and mechanical support, and regulates cell survival, migration, and signaling.

Fibroblasts

The primary connective tissue cells responsible for synthesizing and secreting most extracellular matrix macromolecules, containing an abundant rough endoplasmic reticulum and an extensive Golgi apparatus for collagen processing and trafficking.

Glycosaminoglycans (GAGs)

Long, unbranched carbohydrate chains composed of repeating disaccharide units containing an amino sugar derivative, with at least one sugar bearing a negatively charged carboxylate or sulfate group that attracts $\text{Na}^+$ ions to osmotically trap water and form hydrated gels.

Hyaluronan

The simplest glycosaminoglycan, consisting of up to $25{,}000$ repeating disaccharide units of glucuronic acid and N-acetylglucosamine with a molecular weight of approximately $8 \times 10^6$; it is not covalently linked to a protein core and functions as a space filler, joint lubricant, and aid in wound healing.

Proteoglycan

An ECM macromolecule composed of a core protein covalently attached to glycosaminoglycan (GAG) chains, where carbohydrates can constitute up to $95\%$ of the total molecular weight.

Linkage Tetrasaccharide

A specific four-sugar sequence consisting of xylose, two galactose residues, and glucuronic acid ($\text{xylose}-\text{galactose}-\text{galactose}-\text{glucuronic acid}$) that links a glycosaminoglycan chain to a serine residue of a proteoglycan core protein.

Decorin

A small proteoglycan with a molecular weight of approximately $40{,}000$ that consists of a core protein attached to a single glycosaminoglycan chain.

Aggrecan

A large proteoglycan with a molecular weight of approximately $3 \times 10^6$, composed of a central core protein decorated with numerous chondroitin sulfate and keratan sulfate GAG chains; it is heavily enriched in cartilage.

Aggrecan Aggregate

A massive macromolecular complex in cartilage consisting of many aggrecan monomers non-covalently attached via link proteins to a single continuous hyaluronan molecule.

Collagen

The major insoluble fibrous structural protein accounting for up to $30\%$ of total body protein, characterized by high tensile strength and enriched in tendons, ligaments, cartilage, and the cornea.

Gly-X-Y Sequence

The primary amino acid repeating motif of collagen polypeptides (where $X$ is commonly proline and $Y$ is commonly hydroxyproline) that forms a left-handed helix with $3$ amino acids per turn where every third residue is glycine.

Lysyl Oxidase (LOX)

An extracellular enzyme that oxidizes primary amines on lysine and hydroxylysine residues into reactive aldehydes, which undergo condensation reactions to form covalent cross-links (such as Schiff bases) between collagen fibrils, increasing tissue stiffness.

Procollagen

A triple-helical precursor of collagen synthesized in the endoplasmic reticulum with terminal propeptides that prevent premature intracellular aggregation into fibrils; these propeptides are cleaved by extracellular proteases after secretion.

Elastin

A hydrophobic extracellular matrix protein that forms cross-linked networks of random coils capable of stretching into extended chains under tension and recoiling passively upon relaxation, abundant in arteries, lungs, and skin.

Basal Lamina

A thin, continuous two-dimensional planar sheet of specialized extracellular matrix proteins that supports epithelia (like a rug), forms a sheath or sleeve around muscle and nerve cells, and functions as a semi-permeable selective filter.

Kidney Glomerulus Basal Lamina

A specialized basal lamina positioned between endothelial cells and epithelial cells that acts as a semi-permeable macromolecular filter, retaining blood proteins and nutrients while allowing waste and water to pass into urine.

Laminin

The central heterotrimeric glycoprotein organizer of the basal lamina sheet, composed of $\alpha$, $\beta$, and $\gamma$ chains held together by a coiled-coil domain, with multiple globular arms that bind integrins, dystroglycan, perlecan, nidogen, and self-assemble into planar networks.

Dystrophin

A large rod-shaped cytoskeletal protein in muscle cells that binds intracellular actin filaments to the transmembrane dystroglycan complex; loss-of-function mutations disrupt this mechanical linkage, causing membrane tearing, calcium influx, protease activation, and muscular dystrophy.

Dystroglycan Complex

A transmembrane anchoring complex (comprising $\alpha$- and $\beta$-dystroglycan associated with sarcoglycans, sarcospan, syntrophins, and $\alpha$-dystrobrevin) that links intracellular dystrophin to extracellular laminin-2 in the basal lamina of muscle cells.

Fibronectin

A dimeric extracellular glycoprotein consisting of multidomain polypeptide chains linked near their C-termini by disulfide bonds; it possesses distinct binding domains for collagen, heparin, and cell-surface integrins to mediate cell adhesion, guidance, and signaling.

RGD Sequence

A tripeptide motif consisting of Arginine-Glycine-Aspartate ($\text{Arg}-\text{Gly}-\text{Asp}$) located in the FN-III repeat of fibronectin and other ECM proteins that serves as the primary recognition and binding site for integrin receptors.

Integrins

A family of heterodimeric transmembrane adhesion receptors composed of non-covalently associated $\alpha$ and $\beta$ subunits (formed combinatorially from $18\;\alpha$ genes and $8\;\beta$ genes) that mediate cell adhesion to ECM molecules and transmit bidirectional signals.

$\alpha_5\beta_1$ Integrin

A ubiquitously distributed integrin heterodimer that binds fibronectin; mutation of its $\alpha_5$ subunit results in embryonic death with severe defects in blood vessels, somites, and the neural crest.

$\alpha_{\text{IIb}}\beta_3$ Integrin

An integrin heterodimer expressed on blood platelets that binds fibrinogen; mutation in either subunit impairs platelet aggregation and causes severe bleeding known as Glanzmann disease.

$\alpha_{\text{L}}\beta_2$ Integrin (LFA1)

A leukocyte-specific integrin that binds ICAM1 on endothelial cells to mediate firm arrest and extravasation; mutations in its $\beta_2$ subunit lead to leukocyte adhesion deficiency (LAD) and recurrent infections.

$\alpha_6\beta_4$ Integrin

An integrin heterodimer found in epithelial hemidesmosomes that binds laminin in the basal lamina and connects intracellularly to intermediate filaments; mutations result in severe skin blistering.

Talin

A major cytoskeletal adaptor protein connecting the cytoplasmic tail of integrin $\beta$ subunits to actin filaments; under mechanical tension, talin unfolds to expose cryptic binding sites (including helix 12) that recruit vinculin to reinforce actin attachment.

Vinculin

An intracellular actin-binding adaptor protein recruited to tension-unfolded talin at focal adhesions or extended $\alpha$-catenin at adherens junctions, which binds additional actin filaments to mechanically stabilize the junction.

Focal Adhesion

A specialized cell-matrix anchoring junction where clustered integrins link extracellular matrix components (such as fibronectin) across the plasma membrane to intracellular actin stress fibers via talin, kindlin, and vinculin.

Outside-In Signaling

The signaling pathway triggered when ECM ligands bind the extracellular domain of integrins, causing integrin clustering, cytoskeletal engagement, and activation of cytoplasmic tyrosine kinases such as FAK, which triggers PI3K-Akt and MAPK pathways.

Inside-Out Signaling

A process where intracellular signals from growth factors (via GPCRs or RTKs) activate talin to bind integrin $\beta$ cytoplasmic tails, inducing an extended, high-affinity conformation that allows integrin to bind extracellular ligands.

Anchorage Dependence

The cellular requirement to adhere and spread onto an extracellular matrix to enter the cell cycle and survive; cells kept in suspension or confined to tiny adhesive patches exhibit low probability of entering S phase ($8\%$ vs $90\%$ when well-spread) and undergo apoptosis.

Focal Adhesion Kinase (FAK)

A cytoplasmic non-receptor tyrosine kinase recruited to clustered integrins at focal adhesions that undergoes autophosphorylation and stimulates downstream cascades, including PI3K-Akt and MAPK pathways, promoting cell survival, proliferation, and motility.

P-Selectin

A transmembrane cell adhesion protein on endothelial cells containing a carbohydrate-binding lectin domain that weakly binds oligosaccharides on passing white blood cells, facilitating loose adhesion and rolling along the blood vessel wall.

Matrix Metalloproteinases (MMPs)

A family of approximately $20$ zinc-dependent proteases that digest collagen and other ECM molecules to allow tissue remodeling (e.g., tadpole tail resorption, endometrial shedding) and facilitate tumor cell invasion and metastasis.

Hemidesmosome

A cell-matrix anchoring junction in epithelial cells that anchors intermediate filaments to the basal lamina via $\alpha_6\beta_4$ integrin and type XVII collagen, using intracellular adaptor proteins such as plectin and BP230.

Adherens Junction

A cell-cell anchoring junction mediated by classical cadherins that connects the actin filament networks of adjacent cells via intracellular adaptor proteins including $\alpha$-catenin, $\beta$-catenin, p120-catenin, and vinculin.