Trends in Biochemical Sciences
Dealing with mechanics: mechanisms of force transduction in cells
Section snippets
Soft tissues are subject to a wide range of force
The types of stress (i.e. force per unit area; see Box 1) to which different tissues respond are many, and it is therefore likely that different structures are responsible for different forms of mechanical sensing. For example, cartilage typically experiences stresses of 20 MPa, and the chondrocytes within it alter their expression of gycosaminoglycans and other constituents as they deform in response to such large forces [9]. Bone and the osteocytes within respond to similarly large stresses
Cellular structures that can transmit force
A cellular mechanoresponse requires at least two distinct components: an element or structure that is directly altered by the applied force, and a second element that transmits the information from this ‘mechanical sensor’ to the ultimate target, which might be, for example, a transcription initiation site in the nucleus or cytoplasmic proteins that remodel the cytoskeleton. The second element might also be mechanical or it might involve the same set of intracellular reactions that mediate cell
Internal versus external stress
Not only does mechanosensing involve a response to external forces, but cells also use internally generated stresses to probe the mechanical properties of their environment and show a wide range of responses to extracellular stiffness. Early studies showing that cells can wrinkle the elastic membranes on which they are adhering [52] have been recently expanded by using protein-laminated hydrogels of variable stiffness [7], microfabricated polymer surfaces [53], cantilevers [54] and pedestals
Measuring intracellular mechanics
To clarify force transmission in cells and therefore to evaluate which elements are most likely to deform [56], it is essential to measure the mechanical properties of the cell interior. Cells, like almost all ‘soft’ materials, are characterized by a combination of mechanical properties with features of both solids and liquids. To disentangle this complex behavior and to distinguish between the liquid and solid behavior, mechanical properties are often measured as a function of frequency. A
Outstanding issues and future directions
The general idea that forces can elicit specific cellular responses is increasingly recognized, but the structures first responding to the force are not known. The situation is analogous to knowing that a soluble ligand provokes a specific cellular event but not knowing the receptor for that ligand. Decades of research were required to identify the molecular receptors for ligands as fundamentally important as endotoxin or thrombin, and the task of identifying specific receptors of forces is
Glossary
Glossary
- Elastic:
- A response to force in which the material deforms instantaneously by an amount proportional to the stress, maintains this deformation independent of duration, and recovers to its original unstrained shape when the stress is removed.
- Elastic modulus:
- The ratio of stress to strain, representing a kind of ‘spring constant’ for a material. Because strain has no units, the SI unit for elastic moduli is the Pascal.
- Mechanosensing:
- The ability of a cell or tissue to detect the imposition of a
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