A biomechanical switch regulates the transition towards homeostasis in oesophageal epithelium.

Epithelial cells rapidly adapt their behaviour in response to increasing tissue demands. However, the processes that finely control these cell decisions remain largely unknown. The postnatal period covering the transition between early tissue expansion and the establishment of adult homeostasis provides a convenient model with which to explore this question. Here, we demonstrate that the onset of homeostasis in the epithelium of the mouse oesophagus is guided by the progressive build-up of mechanical strain at the organ level. Single-cell RNA sequencing and whole-organ stretching experiments revealed that the mechanical stress experienced by the growing oesophagus triggers the emergence of a bright Krüppel-like factor 4 (KLF4) committed basal population, which balances cell proliferation and marks the transition towards homeostasis in a yes-associated protein (YAP)-dependent manner. Our results point to a simple mechanism whereby mechanical changes experienced at the whole-tissue level are integrated with those sensed at the cellular level to control epithelial cell fate.

Biologically Inspired, Cell-Selective Release of Aptamer-Trapped Growth Factors by Traction Forces.

Biomaterial scaffolds that are designed to incorporate dynamic, spatiotemporal information have the potential to interface with cells and tissues to direct behavior. Here, a bioinspired, programmable nanotechnology-based platform is described that harnesses cellular traction forces to activate growth factors, eliminating the need for exogenous triggers (e.g., light), spatially diffuse triggers (e.g., enzymes, pH changes), or passive activation (e.g., hydrolysis). Flexible aptamer technology is used to create modular, synthetic mimics of the Large Latent Complex that restrains transforming growth factor-ß1 (TGF-ß1). This flexible nanotechnology-based approach is shown here to work with both platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF-165), integrate with glass coverslips, polyacrylamide gels, and collagen scaffolds, enable activation by various cells (e.g., primary human dermal fibroblasts, HMEC-1 endothelial cells), and unlock fundamentally new capabilities such as selective activation of growth factors by differing cell types (e.g., activation by smooth muscle cells but not fibroblasts) within clinically relevant collagen sponges.