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

Abstract

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.

How the spleen reshapes and retains young and old red blood cells: A computational investigation

“…According to the in vivo observations on the rate spleen by MacDonald et al [13], the transit time of RBCs crossing a slit could range from 0.02 s to 60.5 s, suggesting that the critical area expansion value that triggers lysis in the spleen could vary widely for individual RBCs. Our simulations predict that the cell membrane ruptures when the local area expansion rate exceeds *8%, falling into the range of the critical area expansion for lysis reported in quasistatic and dynamic conditions in experimental [78][79][80][81] and computational [75] studies.…”

“…To assess how the reduced S/V in senescent RBCs would affect their traversal behavior at IES, we simulate the passage of RBCs through IES with surface area of 110 and 100 μm 2 , respectively, representing 15.3% and 23% surface area reduction from our normal RBC cases. The cell volume is still maintained at 90 μm PLOS COMPUTATIONAL BIOLOGY pore formation on membrane patches under stretch were observed in [75][76][77]. Lysis also occurs for other retained RBCs with S/V = 1.11 and 1.22 when the driving pressure gradient is enhanced and the results are summarized in Fig 6 . These results suggest that instead of forcing the retained senescent RBCs cross IES, the excessive pressure gradients cause RBC lysis due to the extreme local area expansion of lipid bilayer.…”

Small molecule therapeutics to destabilize the ACE2-RBD complex: A molecular dynamics study

“…Based on their analysis, among all the drugs listed in the DrugBank database (15), Digitoxin and Nilotinib have the best docking scores with the RBD. In addition to virtual screening techniques, all-atomistic (16,17) and coarse-grained (18)(19)(20) molecular dynamics (MD) methods are effective computational tools for multiscale modeling of virus infection process and computer-aided drug design (21). Deganutti et al (22) employed structure-based screening and supervised MD to find potential drugs that can bind to the druggable pockets of the RBD and inhibit the binding process.…”

Computational investigation of blood cell transport in retinal microaneurysms

“…In the last two decades, numerous multiscale RBC models have been developed to investigate the biological processes associated with RBCs from the protein-level to cellular level, see recent reviews [ 57 – 60 ]. Although the protein-level RBC models, such as [ 61 – 64 ], can be used to assess the altered mechanical properties and morphologies of RBCs induced by either protein defects in blood disorders or virus invasion [ 65 – 70 ], but it is still computationally prohibitive to simulate blood cell suspension or blood flow in the microvessels. Thus, in this work, we employ an efficient cellular level model developed using DPD method to represent RBCs [ 71 , 72 ] and use its extension for platelets [ 29 ].…”