Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping, which imparts an approximately 24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteome-wide screen for rhythmically expressed proteins. We observed temporal coordination of actin regulators that drives cell-intrinsic rhythms in actin dynamics. In consequence, the cellular clock modulates the efficiency of actin-dependent processes such as cell migration and adhesion, which ultimately affect the efficacy of wound healing. Accordingly, skin wounds incurred during a mouse’s active phase exhibited increased fibroblast invasion in vivo and ex vivo, as well as in cultured fibroblasts and keratinocytes. Our experimental results correlate with the observation that the time of injury significantly affects healing after burns in humans, with daytime wounds healing ~60% faster than nighttime wounds. We suggest that circadian regulation of the cytoskeleton influences wound-healing efficacy from the cellular to the organismal scale.

成纤维细胞是伤口愈合的主要细胞主角。它们还表现出昼夜节律计时，这赋予它们的生物功能大约 24 小时的节律。我们使用蛋白质组范围筛选有节奏地表达的蛋白质，研究了成纤维细胞中细胞自主发条的功能后果。我们观察到在肌动蛋白动力学中驱动细胞内在节律的肌动蛋白调节剂的时间协调。因此，细胞时钟调节肌动蛋白依赖性过程的效率，例如细胞迁移和粘附，最终影响伤口愈合的功效。因此，在小鼠活动期发生的皮肤伤口在体内和离体，以及在培养的成纤维细胞和角质形成细胞中表现出增加的成纤维细胞侵袭。我们的实验结果与观察结果相关，即受伤时间显着影响人类烧伤后的愈合，白天伤口的愈合速度比夜间伤口快约 60%。我们认为细胞骨架的昼夜节律调节会影响从细胞到有机体尺度的伤口愈合功效。