Experimental Continuum Mechanics Laboratory, Department of Mechanical and Process Engineering, ETH Zurich, Zurich 8092, Switzerland.
EMPA, Swiss Federal Laboratories for Material Science and Technologies, Überlandstrasse 129, Dübendorf 8600, Switzerland.
Sci Adv. 2023 Apr 7;9(14):eadd1581. doi: 10.1126/sciadv.add1581.
Mammalian cells respond to tactile cues from topographic elements presented by the substrate. Among these, anisotropic features distributed in an ordered manner give directionality. In the extracellular matrix, this ordering is embedded in a noisy environment altering the contact guidance effect. To date, it is unclear how cells respond to topographical signals in a noisy environment. Here, using rationally designed substrates, we report morphotaxis, a guidance mechanism enabling fibroblasts and epithelial cells to move along gradients of topographic order distortion. Isolated cells and cell ensembles perform morphotaxis in response to gradients of different strength and directionality, with mature epithelia integrating variations of topographic order over hundreds of micrometers. The level of topographic order controls cell cycle progression, locally delaying or promoting cell proliferation. In mature epithelia, the combination of morphotaxis and noise-dependent distributed proliferation provides a strategy to enhance wound healing as confirmed by a mathematical model capturing key elements of the process.
哺乳动物细胞会对基质表面呈现的形貌特征所产生的触觉线索做出反应。其中，以有序方式分布的各向异性特征会赋予其方向性。在细胞外基质中，这种有序性嵌入在一个会改变接触导向效应的嘈杂环境中。迄今为止，人们尚不清楚细胞在嘈杂环境中如何响应形貌信号。在这里，我们利用合理设计的基底，报告了形态趋性，这是一种指导机制，使成纤维细胞和上皮细胞能够沿着形貌有序性扭曲的梯度运动。分离的细胞和细胞集落可以响应不同强度和方向的梯度进行形态趋性，成熟的上皮细胞可以整合数百微米范围内形貌有序性的变化。形貌有序性的水平控制着细胞周期的进展，局部延迟或促进细胞增殖。在成熟的上皮细胞中，形态趋性和依赖噪声的分布式增殖的组合为增强伤口愈合提供了一种策略，这一策略得到了一个能够捕获该过程关键要素的数学模型的证实。
