The ECM, Cell Adhesion, and Integrins

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Presentation transcript:

The ECM, Cell Adhesion, and Integrins 2/4/16 Lecture 4, ChE 575

Natural Cell Microenvironment: ECM The extracellular matrix: is made and remodeled by cells that reside within it. is a well-defined composite of proteins and polysaccharides (sugars). regulates cell function (adhesion, survival, migration, etc). contains unique chemical and physical features in each tissue Fibroblasts in connective tissue Molecular Biology of the Cell Epithelial, basal lamina, connective tissue Molecular Biology of the Cell

Sugars (such as hyaluronan) resist compressive forces As well as connect to proteins to provide an organizing structure for cell-ECM signaling

Collagen

Collagens are Chemically and Structurally Diverse Table 19-7 Molecular Biology of the Cell (© Garland Science 2008)

Elastin: five times more extensible than rubber!

Fibronectin Small fibronectin adhesive spots Fibronectin fibers at fibrillar adhesion sites Red: actin microfilaments

Laminin: Critical Organizer of Basal Lamina

The Basal Lamina: architecture of all epithelia

Cells have many different types of receptors

Integrin Structure Integrins are one type of anchoring junction: anchor the cells to the matrix

Many different heterodimers of integrins Heterodimers are specific to the ECM proteins in tissue: matching cell type to tissue 8 betas, 18 alphas = 24 combinations (even though 8x18 = 144)

Not all cells express all integrin pairs! Differential expression of integrins helps isolate cell types to different tissue areas Epithelia: attach to laminin. Carcinoma (epithelial cancer) cells: begin to express fibronectin and collagen-binding integrins, so they can invade the surrounding tissue and metastasize. Tissue engineered material: coat these with proteins that will ONLY BIND the cells you want there!

Integrins undergo conformation changes upon binding RGD: short amino acid sequence that is part of Fibronectin, Vitronectin, Collagen Focal Adhesion Formation Signal!!! Survive, migrate, etc.

Stable bond, survival signals: minimum of 3-5 integrins clustered

Most Cells Need to Adhere and Spread to Survive Geometric Control of Cell Life and Death Christopher S. Chen, et al. Science 276, 1425 (1997);

This effect not from “# of integrin bonds” “anoikis”

Stem Cell Differentiation by controlling size of adhesion sites McBeath et al., Dev Cell, 2004