An understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels with which elasticity can be tuned to approximate that of tissues.
The hypothesis that mechanical factors impact different cell types in fundamentally different ways, and can trigger specific changes similar to those stimulated by soluble ligands, is supported.
A molecular theory that accounts for strain-stiffening in a range of molecularly distinct gels formed from cytoskeletal and extracellular proteins and that reveals universal stress–strain relations at low to intermediate strains is reported.
Within a range of stiffness spanning that of soft tissues, fibroblasts tune their internal stiffness to match that of their substrate, and modulation of cellular stiffness by the rigidity of the environment may be a mechanism used to direct cell migration and wound repair.
Data emphasize the potential importance of material substrate stiffness as a design feature in the next generation of biomaterials intended to promote neuronal regeneration across a lesion in the central nervous system while simultaneously minimizing the ingrowth of astrocytes into the lesion area.
Parallel measurements of the viscoelasticity of tubulin, actin, and vimentin polymers are described and suggest possible specialized roles for the different classes of filaments in vivo.
The three-dimensional intracellular network formed by the filamentous polymers comprising the cytoskeletal affects the way cells sense their extracellular environment and respond to stimuli and can influence ion channel activity at the plasma membrane of cells and conduct mechanical stresses from the cell membrane to internal organelles.
This review presents tantalizing evidence that suggests how binding of selected cytoskeletal proteins to membrane PPIs may promote PPI clustering into raft lipid microdomains, alter their accessibility to other proteins, and even distort the bilayer conformation.
Modulation of the actin crosslinking activity of the MARCKS protein by calmodulin and phosphorylation represents a potential convergence of the calcium–calmodulinand PKC signal transduction pathways in the regulation of theActin cytoskeleton.