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Two-component macrophage model for active phagocytosis with pseudopod formation
Biophysical Journal ( IF 3.4 ) Pub Date : 2024-03-25 , DOI: 10.1016/j.bpj.2024.03.026
Shuo Wang , Shuhao Ma , He Li , Ming Dao , Xuejin Li , George Em Karniadakis

Macrophage phagocytosis is critical for the immune response, homeostasis regulation, and tissue repair. This intricate process involves complex changes in cell morphology, cytoskeletal reorganization, and various receptor-ligand interactions controlled by mechanical constraints. However, there is a lack of comprehensive theoretical and computational models that investigate the mechanical process of phagocytosis in the context of cytoskeletal rearrangement. To address this issue, we propose a novel coarse-grained mesoscopic model that integrates a fluid-like cell membrane and a cytoskeletal network to study the dynamic phagocytosis process. The growth of actin filaments results in the formation of long and thin pseudopods, and the initial cytoskeleton can be disassembled upon target entry and reconstructed after phagocytosis. Through dynamic changes in the cytoskeleton, our macrophage model achieves active phagocytosis by forming a phagocytic cup utilizing pseudopods in two distinct ways. We have developed a new algorithm for modifying membrane area to prevent membrane rupture and ensure sufficient surface area during phagocytosis. In addition, the bending modulus, shear stiffness, and cortical tension of the macrophage model are investigated through computation of the axial force for the tubular structure and micropipette aspiration. With this model, we simulate active phagocytosis at the cytoskeletal level and investigate the mechanical process during the dynamic interplay between macrophage and target particles.

中文翻译:


具有伪足形成的主动吞噬作用的双组分巨噬细胞模型



巨噬细胞吞噬作用对于免疫反应、体内平衡调节和组织修复至关重要。这个复杂的过程涉及细胞形态、细胞骨架重组以及受机械约束控制的各种受体-配体相互作用的复杂变化。然而,缺乏全面的理论和计算模型来研究细胞骨架重排背景下吞噬作用的机械过程。为了解决这个问题,我们提出了一种新颖的粗粒度介观模型,该模型集成了流体状细胞膜和细胞骨架网络来研究动态吞噬过程。肌动蛋白丝的生长导致形成又长又细的伪足,初始细胞骨架可以在进入靶点时分解,并在吞噬作用后重建。通过细胞骨架的动态变化,我们的巨噬细胞模型通过以两种不同的方式利用伪足形成吞噬杯来实现主动吞噬作用。我们开发了一种修改膜面积的新算法,以防止膜破裂并确保吞噬过程中有足够的表面积。此外,通过计算管状结构和微量移液器抽吸的轴向力,研究了巨噬细胞模型的弯曲模量、剪切刚度和皮质张力。通过该模型,我们在细胞骨架水平上模拟主动吞噬作用,并研究巨噬细胞与目标颗粒之间动态相互作用过程中的机械过程。
更新日期:2024-03-25
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