Figure 1. Speculative model of “spring-loaded morphogen” release.

Based on the mechanism proposed by Hinz,¹⁰ this schematic shows that binding of cells via integrins to extracellular matrix proteins, such as collagen and homopentameric COMP, allows cells to detect substrate stiffness, by a brief cytoskeletal contraction that releases growth factors or morphogens. When the ECM is altered by inflammation, proteases, mechanical injury, and/or contraction of neighboring cells, cells may detect it by receptor activation by molecular factors upon contraction. Iterative feedback loops may arise if these factors induce synthesis of new matrix, which may change matrix stiffness and/or sensitivity to inflammatory factors.