Cellular nanoscale stiffness patterns governed by intracellular forces

Cell stiffness measurements have led to insights into various physiological and pathological processes(1,2). Although many cellular behaviors are influenced by intracellular mechanical forces(3–6) that also alter the material properties of the cell, the precise mechanistic relationship between intracellular forces and cell stiffness remains unclear. Here we develop a high spatial resolution cell mechanical imaging platform that reveals the existence of nanoscale stiffness patterns that are governed by intracellular forces. Based on these findings, we develop and validate a cellular mechanical model that quantitatively relates cell stiffness to intracellular forces. This allows us to determine the magnitude of tension within actin bundles, cell cortex, and plasma membrane from the cell stiffness patterns across individual cells. These results expand our knowledge on the mechanical interaction between cells and their environments and offer an alternative approach to determine physiologically-relevant intracellular forces from high-resolution cell stiffness images.