Mechanosensing tensile solid stresses

Experiments and modeling over the past decade have concluded that cells use sophisticated molecular “clutches” at focal adhesions to determine the stiffness of their supporting substrate (1). This mechanism has been shown to modulate a variety of cell functions, including differentiation and migration. In PNAS, Panzetta et al. (2) propose a modification to the existing models, adding mechanical solid stress as an important signaling property.Ever since the discovery that stem cells differentiate into different lineages based on the material properties of their substrate (e.g., neurogenic markers are induced on soft substrates but osteogenic markers are activated on stiff substrates) (3), there have been intense efforts to understand the mechanisms by which cells probe their mechanical environment and respond appropriately. The physical microenvironment guides tissue organization during development but is also important in adult tissue, where cells need to constantly probe the mechanical environment and respond to physical insults or trauma. A familiar example is the response of fibroblasts and epithelium in the vicinity of a wound; these cells sense changes in the tissue mechanics and integrate this information with biochemical signals to migrate and produce tension, closing the wound and reestablishing mechanical homeostasis.Such mechanical sensing and adjustments of cell phenotype contribute to tumor progression, where there are chronic changes in forces and mechanical structure that cause normal cells in and around the growing mass to react to the changing mechanical environment. In most solid tumors, they produce fibrosis (stiffness) and additional forces (solid stresses) that can fuel protumor processes. This is highlighted by recent studies showing that abnormalities in the physical tumor microenvironment contribute to cancer progression and hinder treatment response (4, 5). A better understanding of the genesis of these physical abnormalities has uncovered novel therapeutic targets and enabled new strategies (6, … [↵][1]1To whom correspondence may be addressed: munn{at}steele.mgh.harvard.edu. [1]: #xref-corresp-1-1