In the presence of anisotropic biochemical or topographical patterns, cells tend to align in the direction of these cues—a widely reported phenomenon known as “contact guidance.” To investigate the origins of contact guidance, here, we created substrates micropatterned with parallel lines of fibronectin with dimensions spanning multiple orders of magnitude. Quantitative morphometric analysis of our experimental data reveals two regimes of contact guidance governed by the length scale of the cues that cannot be explained by enforced alignment of focal adhesions. Adopting computational simulations of cell remodeling on inhomogeneous substrates based on a statistical mechanics framework for living cells, we show that contact guidance emerges from anisotropic cell shape fluctuation and “gap avoidance,” i.e., the energetic penalty of cell adhesions on non-adhesive gaps. Our findings therefore point to general biophysical mechanisms underlying cellular contact guidance, without the necessity of invoking specific molecular pathways.

在存在各向异性的生化或地形图案的情况下，细胞倾向于沿这些线索的方向排列，这是一种广泛报道的现象，被称为“接触引导”。为了研究接触指导的起源，在这里，我们创建了由纤连蛋白平行线微图案化的基底，其尺寸跨多个数量级。对我们的实验数据进行的定量形态分析表明，接触指示的两种机制受线索的长度尺度支配，这不能由粘着斑的强制对齐来解释。采用基于活细胞统计力学框架的非均质基质上细胞重塑的计算模拟，我们表明接触指导是由各向异性的细胞形状波动和“空缺避免”产生的，即 细胞粘附在非粘附间隙上的能量损失。因此，我们的发现指向了细胞接触指导下的一般生物物理机制，而无需调用特定的分子途径。