Coarse-Grained Modeling of Pore Dynamics on the Red Blood Cell Membrane under Large Deformations.

Transient pore formation on the membrane of red blood cells (RBCs) under high mechanical tensions is of great importance in many biomedical applications, such as RBC damage (hemolysis) and mechanoporation-based drug delivery. The dynamic process of pore formation, growth, and resealing is hard to visualize in experiments. We developed a mesoscale coarse-grained model to study the characteristics of transient pores on a patch of the lipid bilayer that is strengthened by an elastic meshwork representing the cytoskeleton. Unsteady molecular dynamics was used to study the pore formation and reseal at high strain rates close to the physiological ranges. The critical strain for pore formation, pore characteristics, and cytoskeleton effects were studied. Results show that the presence of the cytoskeleton increases the critical strain of pore formation and confines the pore growth. Moreover, the pore recovery process under negative strain rates (compression) is analyzed. Simulations show that pores can remain open for a long time during the high-speed tank-treading induced stretching and compression process that a patch of the RBC membrane usually experiences under high shear flow. Furthermore, complex loading conditions can affect the pore characteristics and result in denser pores. Finally, the effects of strain rate on pore formation are analyzed. Higher rate stretching of membrane patch can result in a significant increase in the critical areal strain and density of pores. Such a model reveals the dynamic molecular process of RBC damage in biomedical devices and mechanoporation that, to our knowledge, has not been reported before.