  Animal cells in tissues are supported by biopolymer matrices, which typically
exhibit highly nonlinear mechanical properties. While the linear elasticity of
the matrix can significantly impact cell mechanics and functionality, it
remains largely unknown how cells, in turn, affect the nonlinear mechanics of
their surrounding matrix. Here we show that living contractile cells are able
to generate a massive stiffness gradient in three distinct 3D extracellular
matrix model systems: collagen, fibrin, and Matrigel. We decipher this
remarkable behavior by introducing Nonlinear Stress Inference Microscopy
(NSIM), a novel technique to infer stress fields in a 3D matrix from nonlinear
microrheology measurement with optical tweezers. Using NSIM and simulations, we
reveal a long-ranged propagation of cell-generated stresses resulting from
local filament buckling. This slow decay of stress gives rise to the large
spatial extent of the observed cell-induced matrix stiffness gradient, which
could form a mechanism for mechanical communication between cells.
