Intracellular nonequilibrium fluctuating stresses indicate how nonlinear cellular mechanical properties adapt to microenvironmental rigidity

Ming-Tzo Wei,Sabrina S Jedlicka,H Daniel Ou-Yang

doi:10.1038/s41598-020-62567-x

Ming-Tzo Wei, Sabrina S Jedlicka + Show 1 more

Open Access

https://doi.org/10.1038/s41598-020-62567-x

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Abstract

Living cells are known to be in thermodynamically nonequilibrium, which is largely brought about by intracellular molecular motors. The motors consume chemical energies to generate stresses and reorganize the cytoskeleton for the cell to move and divide. However, since there has been a lack of direct measurements characterizing intracellular stresses, questions remained unanswered on the intricacies of how cells use such stresses to regulate their internal mechanical integrity in different microenvironments. This report describes a new experimental approach by which we reveal an environmental rigidity-dependent intracellular stiffness that increases with intracellular stress - a revelation obtained, surprisingly, from a correlation between the fluctuations in cellular stiffness and that of intracellular stresses. More surprisingly, by varying two distinct parameters, environmental rigidity and motor protein activities, we observe that the stiffness-stress relationship follows the same curve. This finding provides some insight into the intricacies by suggesting that cells can regulate their responses to their mechanical microenvironment by adjusting their intracellular stress.

Highlights

Living cells are known to be in thermodynamically nonequilibrium, which is largely brought about by intracellular molecular motors
We demonstrate that intracellular stiffness modulus as a function of intracellular stress obeys a nonlinear curve with power-law dependence by treating intracellular motor proteins
We find that at frequencies lower than about 1 Hz the fluctuations measured by PMR (Ctotal) have a magnitude larger than the expected equilibrium fluctuations based on active microrheology (AMR) (Cequ.) for cells cultured on the stiffer substrate[27] (Fig. 1D)

Summary

Introduction

Living cells are known to be in thermodynamically nonequilibrium, which is largely brought about by intracellular molecular motors. By varying two distinct parameters, environmental rigidity and motor protein activities, we observe that the stiffness-stress relationship follows the same curve. This finding provides some insight into the intricacies by suggesting that cells can regulate their responses to their mechanical microenvironment by adjusting their intracellular stress. We demonstrate that intracellular stiffness modulus as a function of intracellular stress obeys a nonlinear curve with power-law dependence by treating intracellular motor proteins acting on a trapped intracellular probe particle. The data reveal the relationship between molecular dynamics and emergent mesoscale material properties in living cells, inspiring further research on how living systems can take advantage of fluctuations in nonlinear systems

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