Fig. 1: Mechanisms of durotaxis and negative durotaxis.

a Cell migration is directed by extracellular matrix stiffness. Left: the ability of cells to migrate from the soft end to the stiff end of the extracellular matrix is called durotaxis. Right: the ability of cells to migrate from the stiff end to the soft end of the extracellular matrix is called negative durotaxis. b Myosin IIB is unpolarized in cells on a soft matrix, both in 2D and 3D. However, it becomes repolarized as the cells crawl from a soft to a stiff matrix. Cells with unpolarized myosin IIB tend to undergo random migration, whereas cells with polarized myosin IIB exhibit persistent migration. c Focal adhesion exhibits either stable or dynamically fluctuating traction, and the FAK/phosphopaxillin/vinculin pathway is essential for high FA traction and for tugging FA traction over a broad range of ECM rigidities and guide durotaxis. d Filopodia probe the stiffness of the extracellular matrix by using a myosin II-dependent mechanism. The forces generated in lamellipodia are responsible for mechanosensation by regulating the formation of new adhesions. e For cells on stiffness gradient gels, the Golgi–nucleus axis determines the distribution of Golgi microtubules, which in turn regulate focal adhesion turnover. When the Golgi microtubules are disrupted, cells with an unpolarized Golgi and enlarged FAs are unable to migrate against the stiffness gradient. f Cells that exhibit maximal traction force on “optimal stiffness” are capable of moving away from rigid environments and toward matrices on which they can generate more traction, thus exhibiting negative durotaxis.