A theoretical model of efficient phagocytosis driven by curved membrane proteins and active cytoskeleton forces.
A theoretical model of efficient phagocytosis driven by curved membrane proteins and active cytoskeleton forces.
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由弯曲膜蛋白和活跃细胞骨架力驱动的高效吞噬作用的理论模型。
作者：
Sadhu,RajKumar;Barger,SarahR;Penič,Samo;Iglič,Aleš;Krendel,Mira;Gauthier,NilsC;Gov,NirS
吞噬作用是细胞吞噬和内化相对较大颗粒的过程，在我们免疫系统的功能中起着核心作用。我们研究了吞噬作用的过程，考虑一个简化的粗粒模型的三维囊泡，具有均匀的粘附相互作用与刚性颗粒，并含有弯曲的膜结合蛋白质复合物或弯曲的膜纳米结构域，这反过来又招募积极的细胞骨架的力量。当囊泡的弯曲能量消耗被粘附能量的增益平衡时，实现完全吞噬。弯曲（凸形）蛋白质的存在通过在吞噬膜的高度弯曲的前缘处以更高的密度自组织来降低弯曲能量成本，所述吞噬膜形成包裹颗粒的吞噬杯的圆形边缘。这允许在小得多的粘附强度下发生吞没。当弯曲的膜结合蛋白质复合物局部招募肌动蛋白聚合机制，这导致向外的力被施加在膜上，我们发现，吞噬更快地实现，并在较低的蛋白质密度。我们考虑了球形和非球形颗粒，发现非球形颗粒比相同表面积的球形颗粒更难被吞没。对于非球形颗粒，吞噬时间关键取决于颗粒相对于囊泡的初始取向。我们的模型提供了一个机制，在吞噬杯的肌动蛋白细胞骨架的自发自组织，在最近的高分辨率的实验观察，在很好的协议。
Phagocytosis is the process of engulfment and internalization of comparatively large particles by cells, and 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 a uniform adhesion interaction with a rigid particle, and containing curved membrane-bound protein complexes or curved membrane nano-domains, which in turn recruit 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 a 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 membrane-bound protein complexes locally recruit actin polymerization machinery, which leads to outward forces being exerted on the membrane, we found that engulfment is achieved more quickly and at a lower protein density. We consider spherical and non-spherical particles and found 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 on 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.