Nagel Oliver, Guven Can, Theves Matthias, Driscoll Meghan, Losert Wolfgang, Beta Carsten
Institute of Physics und Astronomy, University of Potsdam, Potsdam, Germany.
Department of Physics, University of Maryland, College Park, Maryland, United States of America.
PLoS One. 2014 Dec 10;9(12):e113382. doi: 10.1371/journal.pone.0113382. eCollection 2014.
Motile eukaryotic cells, such as leukocytes, cancer cells, and amoeba, typically move inside the narrow interstitial spacings of tissue or soil. While most of our knowledge of actin-driven eukaryotic motility was obtained from cells that move on planar open surfaces, recent work has demonstrated that confinement can lead to strongly altered motile behavior. Here, we report experimental evidence that motile amoeboid cells undergo a spontaneous symmetry breaking in confined interstitial spaces. Inside narrow channels, the cells switch to a highly persistent, unidirectional mode of motion, moving at a constant speed along the channel. They remain in contact with the two opposing channel side walls and alternate protrusions of their leading edge near each wall. Their actin cytoskeleton exhibits a characteristic arrangement that is dominated by dense, stationary actin foci at the side walls, in conjunction with less dense dynamic regions at the leading edge. Our experimental findings can be explained based on an excitable network model that accounts for the confinement-induced symmetry breaking and correctly recovers the spatio-temporal pattern of protrusions at the leading edge. Since motile cells typically live in the narrow interstitial spacings of tissue or soil, we expect that the geometry-driven polarity we report here plays an important role for movement of cells in their natural environment.
能动的真核细胞,如白细胞、癌细胞和变形虫,通常在组织或土壤狭窄的间质间隙中移动。虽然我们对肌动蛋白驱动的真核细胞运动的大部分了解来自于在平面开放表面上移动的细胞,但最近的研究表明,受限环境会导致运动行为发生显著改变。在这里,我们报告实验证据表明,能动的类变形虫细胞在受限的间质空间中会发生自发的对称性破缺。在狭窄的通道内,细胞切换到一种高度持久的单向运动模式,沿着通道以恒定速度移动。它们与相对的两个通道侧壁保持接触,并在前缘靠近每个壁的位置交替突出。它们的肌动蛋白细胞骨架呈现出一种特征性排列,其主导特征是侧壁处密集、静止的肌动蛋白焦点,以及前缘处密度较低的动态区域。我们的实验结果可以基于一个可激发网络模型来解释,该模型考虑了受限诱导的对称性破缺,并正确地恢复了前缘突出的时空模式。由于能动细胞通常生活在组织或土壤狭窄的间质间隙中,我们预计我们在此报告的几何驱动极性对细胞在其自然环境中的运动起着重要作用。