Adhesion and Mechanotransduction

This lecture covers the structure and mechanics of mammalian cells, including the cytoskeleton, motor proteins, nucleus, plasma membrane, adhesion, modes of migration, mechanosensation, mechanotransduction, Rho signaling, and transcription factors. It delves into actin dynamics, architecture, and mechanics, specialized actin organizations, mesenchymal migration, integrins, ion-channel opening, and the molecular clutch hypothesis. The instructor explains the functional organization of the genome, integrin-mediated mechanotransduction, catch bonds, receptor clustering, and the role of vinculin in forming catch bonds with F-actin. The lecture also explores super-resolution microscopy, the 3D nanoscale architecture of focal adhesions, PALM technology, nuclear mechanotransduction, mechanobiology, and potential mechanisms of nuclear mechanosensing.

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Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them. Cells adhesion occurs from the interactions between cell-adhesion molecules (CAMs), transmembrane proteins located on the cell surface.

Focal adhesion

In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More precisely, focal adhesions are the sub-cellular structures that mediate the regulatory effects (i.e., signaling events) of a cell in response to ECM adhesion. Focal adhesions serve as the mechanical linkages to the ECM, and as a biochemical signaling hub to concentrate and direct numerous signaling proteins at sites of integrin binding and clustering.

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Integrins are transmembrane receptors that help cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane. The presence of integrins allows rapid and flexible responses to events at the cell surface (e.g. signal platelets to initiate an interaction with coagulation factors).

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The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components, microfilaments, intermediate filaments and microtubules, and these are all capable of rapid growth or disassembly dependent on the cell's requirements.

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