Biomechanical Cell Regulation by High Aspect Ratio Nanoimprinted Pillars

High aspect ratio pillared topographies provide a large number of mechanical cues that cells can sense and react to. High aspect ratio pillars have been employed effectively to promote stem cell differentiation and to probe cellular tractions. Yet, the full potential of these topographies for mechanobiology remains insufficiently characterized. Here, the response of progenitor neural stem cells to dense high aspect ratio polymer pillars in the nano- and microscale is investigated. Thermal nanoimprinting is utilized to fabricate with high precision well-defined pillars with high density and aspect ratio. Studies on cell viability, morphology, cell spreading, and migration are performed comparatively to a control flat substrate. The traction forces exerted by the cells on the pillar structures are probed quantitatively by a combined focused ion beam scanning electron microscopy (FIB-SEM) technique. The cell responses observed are distinctive for each dimension, following the trend that an increase in aspect ratio and feature size from nano- to micronscale results in more confined cell morphology with large cytoplasmic penetrations and nuclear deformation. Accordingly, cells seeded on the micrometer scale topography show reduced mobility, a persistent quasi-directional migration, high traction forces, and a lower rate of proliferation. Cells on the nanotopography show higher rate of proliferation, a large cell spread, high mobility with random migration altogether with lower traction forces.