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突起力显微镜揭示了人巨噬细胞足突的振荡力产生和机械敏感性。

Protrusion force microscopy reveals oscillatory force generation and mechanosensing activity of human macrophage podosomes.

机构信息

1] CNRS-IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, F-31077 Toulouse, France [2] Université de Toulouse, UPS (Université Paul Sabatier Toulouse), F-31062 Toulouse, France [3] CNRS-LAAS (Laboratoire d'Analyse et d'Architecture des Systèmes), 7 avenue du colonel Roche, F-31077 Toulouse, France [4] Université de Toulouse, UPS, INSA, INP, ISAE; LAAS, F-31077 Toulouse, France.

1] CNRS-IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, F-31077 Toulouse, France [2] Université de Toulouse, UPS (Université Paul Sabatier Toulouse), F-31062 Toulouse, France.

出版信息

Nat Commun. 2014 Nov 11;5:5343. doi: 10.1038/ncomms6343.

DOI:10.1038/ncomms6343
PMID:25385672
Abstract

Podosomes are adhesion structures formed in monocyte-derived cells. They are F-actin-rich columns perpendicular to the substrate surrounded by a ring of integrins. Here, to measure podosome protrusive forces, we designed an innovative experimental setup named protrusion force microscopy (PFM), which consists in measuring by atomic force microscopy the deformation induced by living cells onto a compliant Formvar sheet. By quantifying the heights of protrusions made by podosomes onto Formvar sheets, we estimate that a single podosome generates a protrusion force that increases with the stiffness of the substratum, which is a hallmark of mechanosensing activity. We show that the protrusive force generated at podosomes oscillates with a constant period and requires combined actomyosin contraction and actin polymerization. Finally, we elaborate a model to explain the mechanical and oscillatory activities of podosomes. Thus, PFM shows that podosomes are mechanosensing cell structures exerting a protrusive force.

摘要

足突是单核细胞衍生细胞中形成的黏附结构。它们是由整合素环绕的、垂直于基质的富含肌动蛋白的柱状物。在这里,为了测量足突的突出力,我们设计了一种名为突出力显微镜(PFM)的创新实验装置,该装置通过原子力显微镜测量活细胞对柔韧的 Formvar 片产生的变形。通过量化足突在 Formvar 片上形成的突起的高度,我们估计单个足突产生的突起力随着基质的刚度增加而增加,这是机械感应活动的标志。我们表明,足突产生的突出力以恒定的周期振荡,需要肌动球蛋白收缩和肌动蛋白聚合的结合。最后,我们详细阐述了一个模型来解释足突的力学和振荡活动。因此,PFM 表明足突是机械感应细胞结构,能够产生突出力。

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