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.

中文翻译：

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大变形下红细胞膜孔隙动力学的粗粒度建模


高机械张力下红细胞 (RBC) 膜上的瞬时孔形成在许多生物医学应用中非常重要，例如红细胞损伤（溶血）和基于机械穿孔的药物输送。孔隙形成、生长和重新密封的动态过程很难在实验中可视化。我们开发了一种中尺度粗粒度模型来研究脂质双层斑块上的瞬时孔的特征，该脂质双层斑块通过代表细胞骨架的弹性网格得到加强。非稳态分子动力学用于研究接近生理范围的高应变率下的孔隙形成和重新密封。研究了孔形成的临界应变、孔特性和细胞骨架效应。结果表明，细胞骨架的存在增加了孔形成的临界应变并限制了孔的生长。此外，还分析了负应变率（压缩）下的孔隙恢复过程。模拟表明，在高速坦克行驶引起的拉伸和压缩过程中，红细胞膜片通常在高剪切流下经历这种拉伸和压缩过程，孔隙可以长时间保持开放状态。此外，复杂的负载条件会影响孔隙特征并导致孔隙更密。最后，分析了应变速率对孔隙形成的影响。膜片的较高拉伸速率会导致临界面积应变和孔密度显着增加。这样的模型揭示了生物医学设备和机械穿孔中红细胞损伤的动态分子过程，据我们所知，以前从未有过报道。