The mechanical cell Current Biology

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The mechanical cell Current Biology Shang-You Tee, Andreas R. Bausch, Paul A. Janmey  Current Biology  Volume 19, Issue 17, Pages R745-R748 (September 2009) DOI: 10.1016/j.cub.2009.06.034 Copyright © 2009 Elsevier Ltd Terms and Conditions

Figure 1 Cellular components proposed to be involved in stiffness sensing. (A) A cell in its resting state. Molecular motors such as non-muscle myosin walk on actin filaments to exert forces through focal adhesion proteins. Focal adhesion proteins are connected to transmembrane proteins such as integrins via slip or catch bonds. Thus, traction forces are transmitted to the external substrate via integrin–ligand interactions. In principle, any protein along this ‘force chain’ of molecular motor to actin to focal adhesion protein to integrin to ligand to extracellular matrix can be stretched and therefore activated. Externally, ligands such as fibronectin or laminin might also be activated by force. On the plasma membrane, integrins or focal adhesion proteins can be stretch activated; the membrane itself may be deformed or sheared to induce protein clustering or recruitment. Internally, the tension on the actin filament itself might affect molecular motor affinity and hence transport of proteins; the nucleus might also be directly deformed to affect transcription. (B) A cell that applies a stress or a strain will get a response that is substrate rigidity dependent. The underlying theme is that the ability of cells to stretch proteins, generate tension and deform membranes or nuclei is strongly influenced by the elasticity of their substrate. Current Biology 2009 19, R745-R748DOI: (10.1016/j.cub.2009.06.034) Copyright © 2009 Elsevier Ltd Terms and Conditions

Figure 2 Change of a cell's shape and elastic modulus with the substrate stiffness. Many cell types change shape depending on the stiffness of their substrate, as illustrated by the two A7 melanoma cells stained for F-actin after incubation on collagen-coated polyacrylamide gels with stiffness of 500 or 15,000 Pa. Under some conditions, such as a fibroblast or melanoma cell adhering to a collagen-coated gel, the cell's apical stiffness measured with an atomic force microscope is approximately equal to that of the substrate as its stiffness is varied from 1 to 10 kPa at which the cell's stiffness reaches a maximum similar to that of the cell culture on glass or plastic, as shown by the dark blue curve The stiffness matching response can be blunted or eliminated by inhibiting myosin, deleting actin crosslinkers like filamin A, or depolymerizing actin, as shown by the light blue curve [11]. Current Biology 2009 19, R745-R748DOI: (10.1016/j.cub.2009.06.034) Copyright © 2009 Elsevier Ltd Terms and Conditions