Theoretical Bases for the Role of Red Blood Cell Shape in the Regulation of Its Volume.

Saša Svetina

doi:10.3389/fphys.2020.00544

Abstract

The red blood cell (RBC) membrane contains a mechanosensitive cation channel Piezo1 that is involved in RBC volume homeostasis. In a recent model of the mechanism of its action it was proposed that Piezo1 cation permeability responds to changes of the RBC shape. The aim here is to review in a descriptive manner different previous studies of RBC behavior that formed the basis for this proposal. These studies include the interpretation of RBC and vesicle shapes based on the minimization of membrane bending energy, the analyses of various consequences of compositional and structural features of RBC membrane, in particular of its membrane skeleton and its integral membrane proteins, and the modeling of the establishment of RBC volume. The proposed model of Piezo1 action is critically evaluated, and a perspective presented for solving some remaining experimental and theoretical problems. Part of the discussion is devoted to the usefulness of theoretical modeling in studies of the behavior of cell systems in general.

Highlights

The red blood cell (RBC) shape is, basically, assumed to depend on the cohesion and mechanical stability of its membrane (Mohandas and Chasis, 1993) and its volume to depend on the harmonized action of several different membrane pumps and channels that define the content of cytoplasm cations (Hoffmann et al, 2009)
The discovery that the RBC membrane includes a mechanosensitive channel, Piezo1, that has an effect on RBC dehydration (Murthy et al, 2017), indicated that RBC volume may depend on membrane mechanics
Piezo1 acts through the activation of Gárdos channels by Ca++ ions that enter the cell when it is open (Cahalan et al, 2015)

Summary

INTRODUCTION

The red blood cell (RBC) shape is, basically, assumed to depend on the cohesion and mechanical stability of its membrane (Mohandas and Chasis, 1993) and its volume to depend on the harmonized action of several different membrane pumps and channels that define the content of cytoplasm cations (Hoffmann et al, 2009). In another study we presented (Svetina et al, 1982) a theoretical counterpart of the earlier proposed bilayer couple hypothesis of RBC shape transformation (Sheetz and Singer, 1974) This led us to formulate a general theory of shapes of vesicular objects with flexible membranes (Svetina and Žekš, 1989). This theory predicted that, among the possible stable shapes, some exhibit polar symmetry We proposed that such shapes could serve as a mechanical origin of cell polarity, and speculated that this could have been realized through curvature dependent interaction between membrane inclusions such as channels and pumps and the surrounding membrane (Svetina and Žekš, 1990; Svetina et al, 1990). Special attention will be devoted to the aspects of RBC population variability It will be shown how the results described in two previous sections can be combined in the model of the effect of Piezo on RBC volume.

THE MECHANICAL AND THERMODYNAMIC BASES OF RBC SHAPE AND DEFORMABILITY

Effects of Compositional and Structural Features of the RBC Membrane

Findings

RBC VOLUME AND RELATED ASPECTS OF THE VARIABILITY OF RBC POPULATION