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19.1: Extracellular matrix

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    Extracellular matrix

    The extracellular matrix consists of a network of substances secreted by cells (figure 19.1). This dynamic structure has many roles in cellular adhesion, signaling, and overall cellular organization.

    Plasma membrane with 3 transmembrane integrins. Microfilaments of the cytoskeleton are bound to the cytoplasmic side. Collagen fibers and fibronectins are bound to the extracellular side. The proteoglycan complex consists of a polysaccharide stem with multiple branched proteins with carbohydrates.

    Figure 19.1: Overview of the extracellular matrix.


    In addition to the many proteins in the matrix, there are some essential carbohydrate components that make up the glycocalyx. This is a carbohydrate "coat" that forms a barrier around the plasma membrane, can bind regulatory factors, and can mediate cell–cell interactions.

    Proteins of the matrix

    The major components of the extracellular matrix form a fibrous, secreted network.


    Fibronectin is a dimer held together by disulfide bonds. These dimers assemble in structural modules that serve as binding sites for other proteins such as heparin, collagen, and fibrin. These proteins are the "matrix" that allows other proteins to dock, and it has RGD loops that serve as integrin binding sites.


    Collagen is synthesized by fibroblasts and is the most abundant protein in the body. There are twenty-seven types of collagen, and it is often a triple helix, stabilized by hydrogen bonding. There are additional nonfibrillar forms that can form web-like structures. Synthesis of collagen requires vitamin C for formation of hydroxyproline.

    As collagen is a major component to connective tissue, it plays key roles in tendons, cornea, blood vessels, hair, and cartilage. Disorders of collagen synthesis are implicated in osteogenesis imperfecta, dwarfism, and skeletal deformities.


    Structurally proteoglycans contain both proteins plus glycosaminoglycans (carbohydrates) and take on a bottle-brush structure (figure 19.1). They assemble into larger complexes, bound to a central hyaluronic acid. The overall structure is negatively charged, which attracts water, allowing it to function as a cushion.


    Laminin consists of three glycoproteins linked through disulfide bonds. They bind cell-surface receptors and are important during development and cell migration.


    Integrins span the plasma membrane and connect the matrix to the cellular environment (inside-out or outside-in signaling). They are associated with fibronectin (RGD sequences) on the extracellular side and have both active and inactive states (figure 19.2).

    COO- domain connected to 4 loops labeled GPIIIa 105 k that feed into the RGD-binding region and end at the bottom NH3+. RGD-binding region: Fibrinogen, fibronectin, v WF, vitronectin. A second COO- domain labeled GPIIb β 25 k, disulfide bridge, loop labeled GPIIa α, multiple loops with Ca2+ touching the RGD-binding region and looping down to NH3+.Figure 19.2: Schematic of integrin structure. The protein spans the plasma membrane and is an extracellular domain that can bind other matrix proteins.

    Matrix metalloproteinases

    The matrix is a dynamic component and is remodeled as a part of normal growth and development. It can also be reorganized as a result of disease or pathology such as arthritis or atherosclerosis.

    A family of enzymes, termed matrix metalloproteinases, is responsible for this remodeling, and they require metal for catalysis. Zinc is the typical cofactor, although some enzymes in the family require cobalt.

    Cell adhesion to the substratum

    Tight junction: Adjacent plasma membranes, strands of transmembrane proteins, intracellular space. Gap junction: Adjacent plasma membranes, gap between cells, connexons (composed of connexins). Anchoring junctions; Desmosome: Adjacent plasma membranes, plaque, transmembrane glycoprotein (cadherin), intermediate filament (keratin), intercellular space. Adherens: Adjacent plasma membranes, plaque, transmembrane glycoprotein (cadherin), actin filament, intracellular space. Hemidesmosome: integrins, basal lamina.

    Figure 19.3: Summary of cell adhesion mechanisms.

    Focal adhesions and hemidesmosomes (figure 19.3) serve to anchor cells to the substratum.

    Focal adhesions are a cluster of rapidly assembling and disassembling proteins that involves a cluster of integrins connected to actin in the cytoskeleton.

    Hemidesmosomes are the tightest of all in vivo attachments. They consist of intermediate filaments (keratin) and form an attachment between the basal surface of epithelial cells to the basement membrane.

    Cell–cell adhesion

    Cells attach to one another through interactions of cell adhesion molecules (CAMs). These interactions can be transient involving one protein on one cell and one on another cell. There are several major classes of CAMs with biological relevance. Their roles are summarized in the table below.

    CAM Characteristics Role
    Selectins (E,L,P) Membrane glycoproteins Bind carbohydrate ligands; transient interactions
    Ig superfamily Calcium independent Modulate interactions with immune cells
    Integrins Interacts with the Ig superfamily RGD domains for interaction with the matrix
    Cadherins Calcium-dependent glycoproteins Join similar cells

    Table 19.1: Major classes of CAMs with biological relevance.

    Cell–cell adhesive junctions

    There are four kinds of connections between cells:

    1. Adherens junctions are composed of cadherins and anchor the cell through interactions with actin filaments.
    2. Tight junctions join adjacent animal cells and function as barriers; they are very important in capillary endothelial cells.
    3. Desmosomes join two cells together through interactions with keratin.
    4. Gap junctions act as channels between cells for direct chemical communication.

    References and resources


    Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.

    Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 7: Interactions between Cells and Their Environment.

    Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 50–51.


    Grey, Kindred, Figure 19.1 Overview of the extracellular matrix. 2021. CC BY 4.0. Adapted from Figure 16. CC BY 4.0. From Open Oregon.

    Grey, Kindred, Figure 19.2 Schematic of integrin structure... 2021. CC BY SA 3.0. Adapted from Integrin by Odysseus1479. CC BY SA 3.0. From Wikimedia Commons.

    Grey, Kindred, Figure 19.3 Summary of cell adhesion mechanisms. 2021. CC BY 3.0. Adapted from 402 Types of Cell Junctions new by OpenStax College. CC BY 3.0. From Wikimedia Commons.

    This page titled 19.1: Extracellular matrix is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by Renee J. LeClair (Virginia Tech Libraries' Open Education Initiative) .

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