The effect of cellular volume regulation on cell physiological functions

Abstract

As an open system, cells can exchange water, ions and energy with the environment, thus the cellular volume and pressure are not constant. In the last decade, cellular volume regulation has attracted intense attention. It has been found that the changes of cell volume can impact many cell physiological processes, such as cell mechanical properties, cell metabolic activities, cell viability and cell growth. However, the mechanisms of cellular volume regulation and how the changes of cell volume affect cell physiological functions are still unclear. In this paper, we will briefly review the mechanisms of cellular volume and pressure regulation, as well as the roles of cellular volume regulation in cancer cell migration, cell adhesion and cell mechanics. The regulation of cellular volume includes the combined effects of the transport of water and ions, as well as the mechanical properties of cytoskeleton. The membrane is permeable to water and the flow of water is driven by the osmotic pressure difference and the hydrostatic pressure difference across the membrane. Since water is incompressible, the transport of water is directly related to the changes in cellular volume. And cells can regulate the ion number (the osmotic pressure) inside the cells by the ion efflux through ion channels and ion pumps. The properties of cytoskeleton can control the activity of ion channels, and then affect the cellular volume regulation. Experiments found that when cells migrate in narrow channels, they can undergo persistent movement in one direction for several hours, and this persistent movement occurs spontaneously in the absence of external gradients. Inhibition of adhesion complexes and cortical contractility do not affect cell migration in narrow channels. In contrast, the adhesion complexes and cortical contractility are the prerequisite of the cell migration on two dimensional substrates since they can provide the traction force for cell migration. Recent theoretical studies and experiments have showed that the water permeation through the cell membrane at leading and trailing edges can provide the driving force for the cell migration in the 3D confined microenvironments. Furthermore, the changes in cell volume can affect the morphology and mechanics of cells adhered between two surfaces. Depending on the cell size, adhesion energy density, the separation of two adhesive surfaces, and the stiffness of the flexible surface, cells can be convex or concave. Furthermore, the changes in volume can directly lead to two unstable adhesion states, i.e., spontaneous rupture and collapse. The changes in cell volume can also affect the detachment of adherent cells. Different changes in cell volume would lead to different detachment behavior for convex cells and concave cells. The cell volume of convex cells decreases during detachment, which is accompanied by a decrease in stretch force. However, the volume of concave cells increases during detachment, and then leads to an increase in stretch force. Moreover, as an open system, the mechanical responds of cells is related to the loading history and the loading rate. This review summaries the mechanisms of cellular volume regulation, emphasizes the importance of water and ion transport in cellular volume regulation, and discusses the regulating roles of cellular volume changes in cancer cell migration, cell adhesion and cell detachment. In conclusion, this review provides an overview of the experimental and theoretical developments on cellular volume regulation, and discusses the current challenges and further prospects of how cellular volume changes affect the cell physiological processes, such as wound healing, cell spreading, membrane trafficking, rigidity sensing, haptotaxis, durotaxis and cell fate determination.