A MULTISCALE MODEL TO STUDY ATP-INDUCED CALCIUM SIGNALING IN LARVAL ZEBRAFISH TAILFIN WOUND RESPONSE

Wound healing is a complex biological process orchestrated by intricate cellular and biochemical interactions. This study leverages a multiscale modeling approach, integrating agent-based and ordinary differential equation (ODE) methods within CompuCell3D, to investigate wound detection and calcium signaling in juvenile zebrafish. Calcium as a ubiquitous secondary messenger plays a crucial role in translating wound stimuli into cellular responses. We focus on the initial phase of wound detection, a multi-step process beginning at the subcellular level with the release of Damage-Associated Molecular Patterns (DAMPs) and subsequent calcium signaling. We hypothesize that an ATP diffusion wave acts as the primary trigger, initiating a downstream calcium signaling cascade mediated by inositol triphosphate (IP3). Calcium and IP3 production and movement from the injured cells to healthy ones would then coordinate a tightly regulated wound response. To investigate this hypothesis, we adapted existing equations from a Drosophila wing disc injury model. We carefully modified them to accurately represent the zebrafish system in our in-silico setup, specifically focusing on relevant agonists. Model predictions were rigorously compared to the zebrafish’s experimental data to validate the computational approach. Our findings provide preliminary evidence suggesting that ATP diffusion through the interstitial spaces of injured tissue may be a potent agonist, triggering localized calcium release closely resembling experimental observations. This multiscale modeling framework offers a promising avenue for significant advancements in wound healing research. It has the potential to facilitate the development of novel therapeutic strategies and discoveries by enabling the integration of cell signaling pathways and tissue engineering.