Mechanical stretch induced collective cell alignment

Cell alignment is a fundamental process in development and plays an essential role in tissue function. Although it has been found that cell alignment exhibits a density-dependent collective behavior, the collective mechanisms within this process remain elusive. In this study, we present a model of collective cell alignment induced by uniaxial mechanical stretch and explore the mechanisms driving this phenomenon. We demonstrate that alignment occurs in a density-dependent manner, with dense cell populations aligning while sparse populations do not. Contrary to previous findings, our results show that this alignment is initiated by substrate deformation upon stretch, which biases cell orientations towards the stretched direction. This deformation-induced alignment occurs passively and simultaneously, allowing us to isolate and identify the factors contributing to the collective behavior. Importantly, we find that once stretched, cells in low-density cultures lose alignment over time, while cells in high-density cultures are able to maintain the alignment level, exhibiting positional adaptation. Furthermore, we observe a self-organization process in high-density cultures, where cells actively reorient towards the stretched direction through cell-cell interactions, enhancing the overall alignment level over time. The emergence of the alignment response has implications for how cell alignment is achieved and sheds light on the cooperative mechanisms underlying collective cell behaviors. Additionally, our findings introduce a novel methodology for aligning cells that could be used for biomedical and tissue engineering applications.