Mapping the mechanical stiffness of live cells with the scanning ion conductance microscope

Mapping the mechanical properties of living cells with high spatial and temporal resolution is important for the exploration of cell function. Widely used imaging techniques such as the atomic force microscope are generally based on direct mechanical contact between the probe and the cell, thereby involving the risk of damaging the cell. Here, we present a noncontact method for fast and quantitative stiffness mapping of living cells with sub-micrometer lateral resolution. This was achieved by repeatedly moving a pressurized nanopipette toward and away from the sample in a scanning ion conductance microscope (SICM). The pressure-induced microfluidic flow through the nanopipette produced a time-varying force on the sample surface, thereby locally indenting it without direct mechanical contact. Maps of sample stiffness (quantified by the Young's modulus) were then determined from ion current approach curves using a finite element model. To demonstrate the capability of the method we visualized the dynamics of individual cytoskeleton fibers in living cells over several hours. Additionally, we found that spreading extensions of migrating fibroblast cells tend to be softer than their lamellum, which is consistent with a mechanism of cell migration by osmotic swelling.