Regulating Cell Adhesion,Cell Detachment,and Cell Mechanical Properties Via Cell Volume

Cells are constantly subjected to the mechanical stimuli came from external environment.The cell volume would change dramatically in response to these external stimuli,since cells lack a stiff cell wall to resist the changes in cell volume.The change of cell volume impacts many cell functions,such as cell mechanical properties,cell metabolic activities,cell viability,and cell differentiation.However,in many studies,cell volume is either assumed to be constant or totally ignored.Thus,studying the mechanisms of cellular volume regulation and how cell volume affects cell functions can help us understand and regulate the cell functions.To perform their physiological functions,cells need to adhere to an extracellular matrix,thus the adhesion between cell and extracellular matrix also plays a critical role in many cell functions.After adhering to a substrate,cells can sense the mechanical properties of the substrate,and then transmit these mechanical information into cell nucleus for further transformation to chemical signals.The mechanical properties of cells play an important role in these processes,since the mechanical properties of cells control the response of cell under mechanical stimuli.However,how the cell volume,cell adhesion,and the mechanical properties of cell affect with each other is still unclear.To answer these questions,we investigate how the changes of cell volume regulate the cell adhesion,cell detachment,and the mechanical properties of cells.In this study,we first investigate how the changes in cell volume affect the shape and dynamics of cells adhered between two surfaces.We show that adherent cells can be either stable(convex or concave)or unstable(spontaneous rupture or collapse),depending on the adhesion energy density,the cell size,the separation of two adhesive surfaces,and the stiffness of the flexible surface.The unstable adherent states are induced directly by the volume regulation.Furthermore,as an open system,the mechanical response of cells is related to the loading history and the loading rate.Secondly,we study how the mechanical and physical properties of substrate control the volume of adherent cells.An increase in substrate stiffness,available spread area,or effective adhesion energy density results in a remarkable cell volume decrease(up to 50%),and the dynamic cell spreading process is also accompanied by dramatic cell volume decrease.The decrease of cell volume is a result of increasing contractility.Stronger interaction between cell and substrate leads to higher actomyosin contractility,expels water and ions,and thus decreases cell volume.Thirdly,we systematically study the roles of cellular volume regulation and bond kinetics in the rate dependence of cell detachment by investigating the cell detachments in the cases of nonspecific adhesion and specific adhesion.We find that the cellular volume regulation and the bond kinetics dominate the rate dependence of cell detachment at different time scales.The bond kinetics contributes more significantly to the rate dependence of the detachment of convex cells,whereas the volume regulation is the predominant contributor of the rate dependence of the detachment of concave cells.Finally,we study how the change of cell volume affect the mechanical properties of cells adhered between two microplates.Under periodic compression,the cells are elastic at high and low compression frequency;but at intermediate compression frequency,the cells are viscoelastic.Furthermore,our theroritical results indicate that the contribution of volume regulation to the cell viscosity is biffer than the contribution of actin cortex.To our knowledge,this is the first study shows that the changes of cell volume can directly induce the unstable adhesion states of cell,and proposes a mechanism of adhesion induced compression of cells.This study also find that the volume regulation is a new origin of the rate dependence of cell detachment and the cell viscoelasticity.Thus our findings can provide insight into the critical role of cell volume in cell adhesion,cell detachment,and the mechanical properties of cells.Our findings also have profound implications for other adhesion-related physiological processes.