Mechanics of neutrophil phagocytosis: experiments and quantitative models
Mechanics of neutrophil phagocytosis: experiments and quantitative models
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DOI：
10.1242/jcs.02876
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发表时间：
2006-05-01
影响因子：
4
通讯作者：
Dembo, Micah
中科院分区：
文献类型：
--
作者：
Herant, Marc;Heinrich, Volkmar;Dembo, Micah
为了定量表征驱动吞噬作用的机械过程，我们观察到最初球形中性粒细胞对直径为3 μ m至11 μ m的抗体包被珠粒的Fc γ R驱动的吞噬。特别是，细胞形态，珠运动和皮质张力的时间过程进行了测定。在这里，我们介绍了一些机制模型的吞噬作用，并测试其有效性，通过比较实验数据与有限元计算多个珠的大小。我们发现，最佳模型涉及两个关键的机械相互作用：细胞骨架和游离膜之间的排斥或压力，驱动突起，和细胞骨架和膜之间的吸引力，新粘附到珠，将细胞变成一个薄的薄片。其他模型，如细胞骨架扩张或肿胀似乎被排除作为吞噬作用的主要驱动因素，因为在吞噬过程中珠运动的特点。我们最后表明，所需的吞噬大珠指向存储在细胞骨架中的应变能超过一个大的距离从前缘（类似于0.5 μ m）的膨胀力，并认为扁平化的力量可以通过已知浓度的非常规肌球蛋白在前缘产生。
To quantitatively characterize the mechanical processes that drive phagocytosis, we observed the Fc gamma R-driven engulfment of antibody-coated beads of diameters 3 mu m to 11 mu m by initially spherical neutrophils. In particular, the time course of cell morphology, of bead motion and of cortical tension were determined. Here, we introduce a number of mechanistic models for phagocytosis and test their validity by comparing the experimental data with finite element computations for multiple bead sizes. We find that the optimal models involve two key mechanical interactions: a repulsion or pressure between cytoskeleton and free membrane that drives protrusion, and an attraction between cytoskeleton and membrane newly adherent to the bead that flattens the cell into a thin lamella. Other models such as cytoskeletal expansion or swelling appear to be ruled out as main drivers of phagocytosis because of the characteristics of bead motion during engulfment. We finally show that the protrusive force necessary for the engulfment of large beads points towards storage of strain energy in the cytoskeleton over a large distance from the leading edge (similar to 0.5 mu m), and that the flattening force can plausibly be generated by the known concentrations of unconventional myosins at the leading edge.