Substrate curvature as a cue to guide spatiotemporal cell and tissue organization.

Recent evidence clearly shows that cells respond to various physical cues in their environments, guiding many cellular processes and tissue morphogenesis, pathology, and repair. One aspect that is gaining significant traction is the role of local geometry as an extracellular cue. Elucidating how geometry affects cell and tissue behavior is, indeed, crucial to design artificial scaffolds and understand tissue growth and remodeling. Perhaps the most fundamental descriptor of local geometry is surface curvature, and a growing body of evidence confirms that surface curvature affects the spatiotemporal organization of cells and tissues. While well-defined in differential geometry, curvature remains somewhat ambiguously treated in biological studies. Here, we provide a more formal curvature framework, based on the notions of mean and Gaussian curvature, and summarize the available evidence on curvature guidance at the cell and tissue levels. We discuss the involved mechanisms, highlighting the interplay between tensile forces and substrate curvature that forms the foundation of curvature guidance. Moreover, we show that relatively simple computational models, based on some application of curvature flow, are able to capture experimental tissue growth remarkably well. Since curvature guidance principles could be leveraged for tissue regeneration, the implications for geometrical scaffold design are also discussed. Finally, perspectives on future research opportunities are provided.