Modeling Diffusion and Vesiculation in Defective Human Erythrocyte Membrane

Abstract

The hemolytic disorders of hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) affect the lives of millions of individuals worldwide. In HS and HE, connections in the vertical and horizontal directions between components of the RBC membrane (see Fig. 1(a)), are disrupted due to defective proteins, leading to loss of the structural and functional integrity of the membrane (1–2). Moreover, disruptions of either the vertical interactions or horizontal interactions affect the lateral diffusivity of the mobile band 3 proteins, as the motion of band 3 in the RBC membrane is confined by the cytoskeleton (3). Although a number of coarse-grained molecular dynamics (CGMD) RBC membrane models have been developed in the past two decades, very few RBC membrane models have been used to study the disordered band 3 diffusion and membrane vesiculation in HS and HE. The implicit representations of either the lipid bilayer or the cytoskeleton in these membrane models limit their applications in the membrane instability problems in HS and HE. In this extended abstract, we develop a two-component CGMD human RBC membrane model that explicitly comprises both the lipid bilayer and the cytoskeleton. In this way, the interactions between the cytoskeleton and the proteins embedded in the lipid bilayer can be simulated. The proposed model allows us to measure the band 3 lateral mobility and simulate the process of membrane vesiculation in the membrane with protein defects.