Theoretical Soft Matter and Biophysics, Institute of Complex Systems and Institute for Advanced Simulation, Forschungszentrum Juelich, D-52425 Juelich, Germany.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, NJ 08544, USA.
Soft Matter. 2019 Aug 14;15(30):6224-6236. doi: 10.1039/c9sm00541b. Epub 2019 Jul 23.
Mechanical properties of the extracellular matrix are important determinants of cellular migration in diverse processes, such as immune response, wound healing, and cancer metastasis. Moreover, recent studies indicate that even bacterial surface colonization can depend on the mechanics of the substrate. Here, we focus on physical mechanisms that can give rise to substrate-rigidity dependent migration. We study a "twitcher", a cell driven by extension-retraction cycles, to idealize bacteria and perhaps eukaryotic cells that employ a slip-stick mode of motion. The twitcher is asymmetric and always pulls itself forward at its front. Analytical calculations show that the migration speed of a twitcher depends non-linearly on substrate rigidity. For soft substrates, deformations do not lead to build-up of significant force and the migration speed is therefore determined by stochastic adhesion unbinding. For rigid substrates, forced adhesion rupture determines the migration speed. Depending on the force-sensitivity of front and rear adhesions, forced bond rupture implies an increase or a decrease of the migration speed. A requirement for the occurrence of rigidity-dependent stick-slip migration is a "sticky" substrate, with binding rates being an order of magnitude larger than unbinding rates in absence of force. Computer simulations show that small stall forces of the driving machinery lead to a reduced movement on high rigidities, regardless of force-sensitivities of bonds. The simulations also confirm the occurrence of rigidity-dependent migration speed in a generic model for slip-stick migration of cells on a sticky substrate.
细胞外基质的力学特性是细胞在多种过程中迁移的重要决定因素，如免疫反应、伤口愈合和癌症转移。此外，最近的研究表明，即使是细菌表面的定殖也可能依赖于基质的力学性质。在这里，我们关注的是可以导致基底刚性依赖性迁移的物理机制。我们研究了一种“抽搐器”，一种由延伸-回缩循环驱动的细胞，以理想化细菌，也许是采用滑动-粘着运动模式的真核细胞。抽搐器是不对称的，总是在其前端将自己向前拉。分析计算表明，抽搐器的迁移速度与基质的刚性呈非线性关系。对于软基底，变形不会导致显著力的积累，因此迁移速度由随机粘附解吸决定。对于刚性基底，强制粘附断裂决定了迁移速度。根据前后附着的力敏感性，强制键断裂意味着迁移速度的增加或减少。刚性依赖性粘滑迁移发生的一个要求是“粘性”基底，在没有力的情况下，结合速率比解吸速率大一个数量级。计算机模拟表明，驱动机构的小停顿力会导致在高刚性下的运动减少，而不管键的力敏感性如何。模拟还证实了在粘性基底上粘性滑动细胞迁移的通用模型中存在刚性依赖性迁移速度。
