Institut Pasteur, Bioimage Analysis Unit, Paris, France.
CNRS UMR3691, Paris, France.
Sci Rep. 2017 Aug 23;7(1):9178. doi: 10.1038/s41598-017-09240-y.
Cell motility is governed by a complex molecular machinery that converts physico-chemical cues into whole-cell movement. Understanding the underlying biophysical mechanisms requires the ability to measure physical quantities inside the cell in a simple, reproducible and preferably non-invasive manner. To this end, we developed BioFlow, a computational mechano-imaging method and associated software able to extract intracellular measurements including pressure, forces and velocity everywhere inside freely moving cells in two and three dimensions with high spatial resolution in a non-invasive manner. This is achieved by extracting the motion of intracellular material observed using fluorescence microscopy, while simultaneously inferring the parameters of a given theoretical model of the cell interior. We illustrate the power of BioFlow in the context of amoeboid cell migration, by modelling the intracellular actin bulk flow of the parasite Entamoeba histolytica using fluid dynamics, and report unique experimental measures that complement and extend both theoretical estimations and invasive experimental measures. Thanks to its flexibility, BioFlow is easily adaptable to other theoretical models of the cell, and alleviates the need for complex or invasive experimental conditions, thus constituting a powerful tool-kit for mechano-biology studies. BioFlow is open-source and freely available via the Icy software.
细胞运动受复杂的分子机制调控,该机制将理化线索转化为整个细胞的运动。理解潜在的生物物理机制需要能够以简单、可重复且最好是非侵入性的方式测量细胞内的物理量。为此,我们开发了 BioFlow,这是一种计算力学成像方法和相关软件,能够以非侵入性方式以高空间分辨率在二维和三维空间中提取包括压力、力和速度在内的细胞内测量值,这些测量值来自于自由运动细胞的任何位置。这是通过提取使用荧光显微镜观察到的细胞内物质的运动来实现的,同时同时推断给定细胞内部理论模型的参数。我们通过使用流体动力学来模拟寄生虫溶组织内阿米巴的细胞内肌动蛋白主体流动,在变形虫细胞迁移的背景下说明了 BioFlow 的强大功能,并报告了独特的实验测量值,这些测量值补充和扩展了理论估计和侵入性实验测量值。由于其灵活性,BioFlow 易于适应其他细胞的理论模型,并减轻了对复杂或侵入性实验条件的需求,因此它构成了机械生物学研究的强大工具包。BioFlow 是开源的,并可通过 Icy 软件免费获得。