从咬噬到吞噬:靶标力学通过曲率 - 肌动蛋白耦合决定吞噬模式
From biting to engulfment: Target mechanics determines modes of phagocytosis through curvature--actin coupling
AI总结:
研究靶标力学在吞噬作用中的角色,通过理论建模与实验结合,开发膜模拟框架,揭示随靶标硬度增加有咬噬、推挤、完全吞噬三种力学状态,并经实验验证,确定靶标力学是清除及细胞间相互作用的关键调节因子。
摘要:
吞噬作用是清除具有广泛力学性质靶标的核心先天免疫过程,但靶标力学在识别和吞噬中的作用尚不清楚。本文结合理论建模与实验,揭示靶标硬度如何控制吞噬细胞与靶标相互作用的不同模式。开发了基于膜的模拟框架,其中吞噬细胞及其靶标均可变形并发生大的形状变化,肌动蛋白驱动的突起由曲率敏感膜复合物调节。模型预测随靶标硬度增加有三种力学状态:一是咬噬(胞咬作用),提取部分靶标;二是推挤,靶标移位而非被吞噬;三是完全吞噬。通过体内凋亡靶标的上皮清除、巨噬细胞对巨型单层囊泡和淋巴瘤细胞的吞噬验证了这些预测。结果表明靶标力学是清除和细胞间相互作用的关键调节因子。
英文摘要:
Phagocytosis is a core innate immune process that clears targets spanning a wide range of mechanical properties, yet the role of target mechanics in recognition and engulfment remains unclear. Here, we combine theoretical modeling and experiments to reveal how target stiffness governs distinct modes of phagocyte--target interaction. We develop a membrane-based simulation framework in which both the engulfing cell and its target are deformable and undergo large shape changes, while actin-driven protrusions are regulated by curvature-sensitive membrane complexes. The model predicts three mechanical regimes with increasing target stiffness: (i) biting (trogocytosis), where part of the target is extracted; (ii) pushing, where the target is displaced rather than engulfed; and (iii) complete engulfment. We validate these predictions in epithelial clearance of apoptotic targets in vivo and macrophage engulfment of Giant Unilamellar Vesicles (GUVs) and lymphoma cells. Together, our results identify target mechanics as a key regulator of clearance and cell--cell interactions.
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