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中性粒细胞吞噬作用的机制:实验与定量模型

Mechanics of neutrophil phagocytosis: experiments and quantitative models.

作者信息

Herant Marc, Heinrich Volkmar, Dembo Micah

机构信息

Biomedical Engineering Department, Boston University, 44 Cummington Street, Boston, MA 02215, USA.

出版信息

J Cell Sci. 2006 May 1;119(Pt 9):1903-13. doi: 10.1242/jcs.02876.

Abstract

To quantitatively characterize the mechanical processes that drive phagocytosis, we observed the FcgammaR-driven engulfment of antibody-coated beads of diameters 3 mum to 11 mum 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 ( approximately 0.5 microm), and that the flattening force can plausibly be generated by the known concentrations of unconventional myosins at the leading edge.

摘要

为了定量表征驱动吞噬作用的力学过程,我们观察了初始呈球形的中性粒细胞通过FcγR介导对直径为3微米至11微米的抗体包被微珠的吞噬。特别地,确定了细胞形态、微珠运动和皮质张力随时间的变化过程。在此,我们介绍了一些吞噬作用的力学模型,并通过将实验数据与多种微珠尺寸的有限元计算结果进行比较来检验其有效性。我们发现,最优模型涉及两个关键的力学相互作用:细胞骨架与自由膜之间的排斥力或压力驱动突起形成,以及细胞骨架与新附着在微珠上的膜之间的吸引力使细胞扁平形成薄片。由于吞噬过程中微珠运动的特性,诸如细胞骨架扩张或肿胀等其他模型似乎被排除在吞噬作用的主要驱动因素之外。我们最终表明,吞噬大微珠所需的突出力指向细胞骨架中从前缘起一段较大距离(约0.5微米)上应变能的储存,并且扁平力可能由前缘处已知浓度的非常规肌球蛋白产生。

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