A computational model for single cell Lamin-A structural organization after microfluidic compression.

Abstract

In recent years, nuclear mechanobiology gained a lot of attention for the study of cell responses to external cues like adhesive forces, applied compression, and/or shear-stresses. In details, the Lamin-A protein-as major constituent of the cell nucleus structure-plays a crucial role in the overall nucleus mechanobiological response. However, modeling and analysis of Lamin-A protein organization upon rapid compression conditions in microfluidics are still difficult to be performed. Here, we introduce the possibility to control an applied microfluidic compression on single cells, deforming them up to the nucleus level. In a wide range of stresses (~1-102 kPa) applied on healthy and cancer cells, we report increasing Lamin-A intensities which scale as a power law with the applied compression. Then, an increase up to two times of the nuclear viscosity is measured in healthy cells, due to the modified Lamin-A organization. This is ascribable to the increasing assembly of Lamin-A filament-like branches which increment both in number and elongation (up to branches four-timelonger). Moreover, the solution of a computational model of differential equations is presented as a powerful tool for a single cell prediction of the Lamin-A assembly as a function of the applied compression.