Vertical Nanopillars as Probes for in Situ Nuclear Mechanotransduction

The stability and deformability of the cell nucleus are important to many biological processes like migration, proliferation, polarization. When cells are exposed to mechanical force, the force will be transmitted via cytoskeleton to the nucleus, induce shape deformation of the nuclear envelopes, and even change the configurations of nucleoskeletons. However, current techniques for studying nuclear mechanics are limited for studying inducing the effects of subcellular force perturbation in live cells. Here we developed a novel assay of using vertical nanopillar arrays to study the mechanical coupling between cell nucleus and cytoskeleton in live cells. Our results showed that nanopillars can induce deformation of nuclear envelope. By changing the geometry of the nanopillars or the stiffness of the nucleus, we can control the degree of nuclear deformation. Also, cytoskeletons such as actin and intermediate filaments were showed to play important roles in inducing and preventing nuclear deformation, respectively. Furthermore, we showed that mechanical perturbation of the nuclear envelope can cause the reorganization of nuclear lamina, which give the clue that cell nucleus itself may be able to sense and respond to mechanical signals. Overall, vertical nanopillars provide a long-term and non-invasive force to create a subcellular nuclear perturbation, and can be used as a tool for studying nuclear mechanotransduction in live cells.