Active nano-mechanical stimulation of single cells for mechanobiology

TL;DR

This paper presents a novel active nano-mechanical platform using Fe-coated micropillars and magnetic fields to precisely stimulate living cells, enabling detailed study of cellular mechanotransduction mechanisms.

Contribution

Introduction of a new magnetic-actuated micropillar platform for controlled nano-mechanical stimulation of cells in vitro.

Findings

Nano-mechanical stimuli influence actin cytoskeleton organization.

Mechanical stimulation affects nuclear morphology and histone dynamics.

Stimuli induce translocation of MKL transcription-cofactor.

Abstract

In-vivo, cells are frequently exposed to multiple mechanical stimuli arising from the extracellular microenvironment, with deep impact on many biological functions. On the other hand, current methods for mechanobiology do not allow to easily replicate in-vitro the complex spatio-temporal behavior of such mechanical signals. Here, we introduce a new platform for studying the mechanical coupling between the extracellular environment and the nucleus in living cells, based on active substrates for cell culture made of Fe-coated polymeric micropillars. Under the action of quasi-static external magnetic fields, each group of pillars produces synchronous nano-mechanical stimuli at different points of the cell membrane, thanks to the highly controllable pillars' deflection. This method enables to perform a new set of experiments for the investigation of cellular dynamics and mechanotransduction mechanisms in response to a periodic nano-pinching, with tunable strength and arbitrary temporal shape. We applied this methodology to NIH3T3 cells, demonstrating how the nano-mechanical stimulation affects the actin cytoskeleton, nuclear morphology, H2B core-histone dynamics and MKL transcription-cofactor nuclear to cytoplasmic translocation.