Mechanical waves decode wound size information to coordinate epidermal cell migration in zebrafish

Marco de Leon^1*, Fu-Lai Wen², Hsiao-Yuh Roan¹, Ying-Ting Wang¹, Chung-Han Wang¹, Keng-Hui Lin², Chen-Hui Chen¹

¹Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan, Taiwan
²Institute of Physics, Academia Sinica, Taipei, Taiwan, Taiwan

* Presenter:Marco de Leon, email:marcopdeleon@gate.sinica.edu.tw

In highly regenerative animals, such as salamanders and zebrafish, rapid wound healing is crucial to jumpstart regeneration. However, the process by which epithelial cells are efficiently recruited to cover stump wounds of varying size remains poorly understood. Here we show that in adult zebrafish, tailfin amputation triggers a mechanical wave that is able to anticipate wound sizes for coordinating cell migration on a millimeter scale. Using live in toto monitoring of several thousands of basal epithelial cells (BECs) near the wound edge, we found that migrating BECs systematically form an advancing cell mobilization zones (CMZs), which propagate at a constant speed of 4-5 μm/min. Remarkably, amputating tailfins at different levels proportionally regulated the CMZ length and the maximum distance traveled by each CMZ. A simple One-Dimensional Active Spring (ODAS) model captured key CMZ features observed in vivo, and faithfully, predicted CMZ responses to experimental perturbations. Furthermore, we found that injury-induced reactive oxygen species (ROS), presumably BEC-derived hydrogen peroxide, can fine-tune the CMZ length to communicate wound size information. Taken together, our findings identify a wound healing mechanism that couples a local chemical signal with a far-reaching mechanical wave. This simple yet tunable tactic enables highly regenerative animals to mount synchronized tissue-scale cell responses that are matched at scale for healing stump wounds of different size.

Keywords: Wound healing, Collective cell migration, One-dimensional active spring model, Mechanical wave, Reactive oxygen species