Intermediate filament-deficient cells are mechanically softer at large deformation: a multi-scale simulation study

Abstract

The cell's cytoskeleton, providing cells with structure and shape, consists of different structural proteins, including microtubules, actin microfilaments and intermediate filaments. It has been suggested that intermediate filaments play a crucial role in providing mechanical stability to cells. By utilizing a simple coarse-grained computational model of the intermediate filament network in eukaryotic cells, we show here that intermediate filaments play a significant role in the cell mechanical behavior at large deformation, and reveal mechanistic insight into cell deformation under varying intermediate filament densities. We find that intermediate filament-deficient cells display an altered mechanical behavior, featuring a softer mechanical response at large deformation while the mechanical properties remain largely unchanged under small deformation. We compare the results with experimental studies in vimentin-deficient cells, showing good qualitative agreement. Our results suggest that intermediate filaments contribute to cell stiffness and deformation at large deformation, and thus play a significant role in maintaining cell structural integrity in response to applied stress and strain, in agreement with earlier hypotheses. The simulation results also suggest that changes in the filament density result in profound alterations of the deformation state of the cell nucleus, leading to greater stretch in the direction of loading and greater contraction in the orthogonal direction as the intermediate filament density is increased. Our model opens the door to future studies to investigate disease states, the effects of amino acid mutations and how structural changes at different levels in the cell's structural makeup influence biomechanical properties.