Simulation of the defective erythrocyte membrane
HE LI (UCONN), George Lykotrafitis (University of Connecticut)
Mechanics and Physics of Biological Cells
Mon 9:00 - 10:30
Barus-Holley 166
The common etiology of hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) is the decreased deformability and increased fragility of red blood cells (RBCs) resulting in a short life span and a compromised function of RBCs. In HS, vertical interactions between the cytoskeleton and the lipid bilayer are disrupted, due to defective membrane proteins, leading to loss of structural and functional integrity of the RBC membrane. In HE, horizontal interactions within the cytoskeleton are defective. Here, we introduce a two-component coarse-grained molecular dynamics model for the human RBC membrane that explicitly includes both the lipid bilayer and the cytoskeleton. The proposed model allows us to measure the band 3 lateral mobility and simulate the process of membrane loss. The lipid bilayer comprises three types of coarse-grained particles. Lipid particles represent a cluster of lipid molecules, glycophorin particles denote glycophorin proteins, and band 3 particles represent band 3 complexes. The spectrin filaments of the RBC cytoskeleton are represented by particles connected by unbreakable springs. The spectrin filaments are connected to the actin junctions forming a canonical hexagonal network. The Nose-Hoover thermostat is used. First, we study the variations in the diffusion of band 3 caused by defects in membrane proteins related to HS and HE. Second, we simulate the behavior of the membrane under compression and study the mechanism of membrane loss in HS. Our simulations show that the cytoskeleton connectivity is the major determinant of the lateral diffusion of band 3 in the erythrocyte membrane and that vesiculation results mainly from defective interactions between the lipid bilayer and the erythrocyte cytoskeleton, not from the distribution of band 3 proteins. The proposed model can be broadly applied in the study of a variety of situations involving defective RBC membrane such as in the sickle cell disease and in the modeling of RBC adhesion.