Extracellular Matrix and Extracellular Interactions

• Extracellular interactions allow for cells to communicate with each other and respond to external stimuli.

Extracellular Matrix §

• The extracellular matrix (ECM) consists of an organized network of secreted molecules that provides scaffolding and plays a regulatory role for cellular activity and shape.
  • The ECM tends to be made of extended fibrous protein which self-assemble into a three-dimensional network.
  • The ECM is a dynamic structure which undergoes mechanical motion, as well as continued degradation and reconstruction.
    • The degradation is accomplished through matrix metalloproteinases (MMPs). which digest nearly all the ECM components, though to be for tissue remodeling and restructuring.
  • Mechanotransduction - the process of converting mechanical stimuli chemical signals in the cytoplasm.
    • It is thought to be mediated by the stretching of some adaptor proteins, which exposes additional blinding sites .

Components §

• Collagens - fibrous glycoproteins with notably high tensile strength. They contain triple helixes of chains (Type I, II, III) and possibly or nonhelical segments interspersed along the molecule with globular domains on each end (Type IV).
  • Fibrillar Collagens - assemble into rigid rope-like fibrils which can be packaged into thicker fibers.
  • They provide the insoluble framework for the mechanical properties of the extracellular matrix.
• Proteoglycans - a protein-polysaccharide complex which may be assembled into giant complexes. They form a porous, hydrated gel that occupies the extracellular space to resist crushing forces.
  • They are thought to have a role in cell-to-cell signaling.
• Fibronectin - consists of a linear array of distinct building blocks. They facilitate the interactions between ECM components and between cells and receptors.
  • Fibronectin also facilitates cell migration. Cells tend to migrate on fibronectin surfaces
  • Because they are made of building blocks, they tend to have a modular function.
• Laminin - glycoproteins which play a role in a cell’s potential for migration, growth, and differentiation.
• Integrins - membrane proteins found in animal cells that play a key role in integrating extracellular and intracellular activities.
  • They can bind to ligands on the outside of the cell.
  • They can also interact with proteins within the cell to influence cellular activity.
  • Integrins usually lie in an inactive bent state, but when a specific ligand binds to them, they become straight and active. Thus, they act as receptors.
    • Inside Out Signaling - cytoplasmic molecules induce a conformational change in the integrin. When multiple integrins are activated this way, the cell surface more strongly interacts with the extracellular ligands.
    • Outside In Signals - the integrin’s extracellular domain binds to a ligand which induces a conformational change on its cytoplasmic side, triggering cytoplasmic proteins in the process.
    • They have the RGD sequence which helps many extracellular proteins bind to them.

Extracellular Interactions §

Integrin-Based and Cell-ECM §

• Focal Adhesions are dynamic structures that are assembled when a cell makes contact with a surface and spreads itself.
  • This plays a role in cell locomotion by creating mechanical forces or responding to such forces. It helps that the structure contains actin and myosin.
• Hemidesmosomes - contains a dense plaque on the inner surface of the plasma membrane with filaments coursing outward into the cytoplasm. Its filaments tend to consist of keratin and are thicker than focal adhesions.
  • The keratin intermediate filaments serve to support the cell.
  • They are linked to the ECM via integrins.

Cadherin-Based and Cell-Cell §

• Adherens junctions - they involve cells held together by calcium-dependent linkages formed between the extracellular domains of cadherin molecules.
  • They connect the external environment to the actin cytoskeleton.
  • They provide a pathway for signals to be transmitted from the cell to the exterior of the cytoplasm
• Desmosomes - Disk shaped adhesive junctions, particularly found in tissues subject to mechanical stress. They contain cadherins that link two cells.
  • The cadherins involved in desmosome formation are called desmogelins and desmocollins.
  • These cadherins bind to each other in extracellular space, and are anchored to intermediate filaments in cytoplasmic space.

Interactions with Other Cells §

• Cells have shown the ability to recognize other cell surfaces, selectively adhering to some surfaces. Animal tissue has shown the ability of cells to self-assemble into organized structures.
• Cell adhesion also allows for transmembrane signaling wherein information is transferred across the plasma membrane. This, in turn, influences cellular activity.

Proteins involved in Cell Adhesion. §

• Selectins - a family of integral membrane glycoproteins that recognize and bind to a particular arrangement of sugars in the oligosaccharides projecting from the surface of other cells.
  • The binding of selectins to sugars requires calcium.
• (Certain) Immunoglobulins - a family of proteins with modular construction that have a role in the immune system, but also facilitate calcium independent cell-cell adhesion.
• (Certain) Integrins - some integrins mediate cell-cell adhesion by binding to proteins on other cells.
• Cadherins - a family of glycoproteins that mediate calcium dependent cell-cell adhesion..
  • They also transmit signals from the ECM to the cytoplasm.
  • They tend to join cells of similar type to one another by binding to the same cadherins on the surface of the neighboring cell. They are thought to be responsible for self-sorting of mixed aggregates.
    • They tend to associate laterally to form parallel dimers and making use of calcium ion bridges for rigidity.
    • They may undergo interdigitation where bonded cadherins configure like a zipper. This gives the adhesion more rigidity.
  • They tend to have a modular construction.
  • Catenins in the cytosol tether the cadherins to the cytoskeleton, in addition to transmitting signals from the cytoplasm to the nucleus.

Junctions §

Tight Junctions (zonulae occludens) §

• Located on the apical end of the junctional complex between ajacent epithelial cells,
• They block diffusion through the paracellular pathway (intracellular space) between cells.
  • That said, they are selectively permeable to some solutes and ions.
  • The junctions can also be used to hold water on one side of the cell sheet.
• It consists of paired rows of aligned integral member proteins forming continuous fibrils that forms a gasket around cells.
• They primarily consist of claudins and sometimes occludins.

Gap Junctions §

• Specialized sites of communication between adjoining cells in animal cells.
• They are sites where the plasma membranes of adjacent cells come very close but not touching each other
• Contains ion channels that connect the cytoplasms of cells.
• They are composed entirely of connexin organized into complexes called connexons that span the membrane channel.
  • Connexons consist of a ring around an annulus.
  • Connexons tend to be clustered in specific regions of the membrane which form plaques. As a result, they connect many cells of a tissue together.
• They are relatively nonselective compared to the plasma membrane’s ion channels. They can also be gated and triggered by stimuli.
• They allow cells to cooperate metabolically or respond synchronously from stimulation of a few cells in the network.

Plasmodemsata §

• Sites of communication between adjacent plant cells.
• Contains channels that connect the cytoplasm of cells to allow the passage of solutes.
• They are lined by plasma membrane and contain a dense central structure called the desmotubule.
  • The desmotubule is derived from the smooth endoplasmic reticulum of two cells.
• The plasmodesmata pore is capable of dilation, allowing large solutes to pass through.
• Movement proteins regulate the flow of proteins across the plasmodesmata.

Tunneling Nanotubes §

• Thin, highly elongated tubules that connect cells over long distances.

Links §

• Karp Ch. 7

  • Ch. 7.3 - an overview for the components of the extracellular matrix.
  • Ch. 7.6 - more on Hemidesmosomes and Focal Adhesions
  • Ch. 7.7 - more on the proteins involved in Cell-Cell Adhesion

• Plasma Membrane - more on membranes.

• Cell Wall - more on cell walls