论文标题
由弯曲膜蛋白和活性细胞骨架力驱动的有效吞噬作用的理论模型
Theoretical model of efficient phagocytosis driven by curved membrane proteins and active cytoskeleton forces
论文作者
论文摘要
吞噬作用是细胞相对较大的颗粒吞噬和内在化的过程,在我们的免疫系统的功能中起着核心作用。我们通过考虑在存在弯曲的膜蛋白和活性细胞骨骼力的情况下,考虑了三维囊泡的简化粗粒粒模型,研究了吞噬作用的过程。当囊泡的弯曲能量通过粘附能的增益平衡时,就可以实现完全的吞噬。弯曲(凸)蛋白的存在通过在吞噬膜的高度弯曲的前缘进行自组织来降低弯曲能量成本,该膜形成了吞噬杯的圆形边缘,该吞噬杯围绕粒子包裹。这使吞噬的粘附力强度要小得多。当弯曲的蛋白质向外施加代表肌动蛋白聚合的伸出力时,在前缘,我们发现吞噬量更快,较低的蛋白质密度。我们考虑球形和非球形颗粒,发现与同一表面积的球形颗粒相比,非球形颗粒更难吞噬。对于非球形颗粒,吞噬时间至关重要取决于粒子相对于囊泡的初始方向。我们的模型提供了一种机制,可以使吞噬杯中肌动蛋白细胞骨架自发自组织,与最近的高分辨率实验观察结果很好地吻合。
Phagocytosis is the process of engulfment and internalization of comparatively large particles by the cell, that plays a central role in the functioning of our immune system. We study the process of phagocytosis by considering a simplified coarse grained model of a three-dimensional vesicle, having uniform adhesion interaction with a rigid particle, in the presence of curved membrane proteins and active cytoskeletal forces. Complete engulfment is achieved when the bending energy cost of the vesicle is balanced by the gain in the adhesion energy. The presence of curved (convex) proteins reduces the bending energy cost by self-organizing with higher density at the highly curved leading edge of the engulfing membrane, which forms the circular rim of the phagocytic cup that wraps around the particle. This allows the engulfment to occur at much smaller adhesion strength. When the curved proteins exert outwards protrusive forces, representing actin polymerization, at the leading edge, we find that engulfment is achieved more quickly and at lower protein density. We consider spherical as well as non-spherical particles, and find that non-spherical particles are more difficult to engulf in comparison to the spherical particles of the same surface area. For non-spherical particles, the engulfment time crucially depends upon the initial orientation of the particles with respect to the vesicle. Our model offers a mechanism for the spontaneous self-organization of the actin cytoskeleton at the phagocytic cup, in good agreement with recent high-resolution experimental observations.