Computational models for wound healing

During wound closure in biological tissues, cells exhibit a set of fundamental mechanisms: cell migration, reorganization, lemellipodia and filopodia motility, and biochemical regulation through actin and ion flow, among others. The closure requires the synchronisation of these processes, which have been so far studied independently, either from the experimental or the computational standpoint. Although it has been possible to determine and correlate the relevant proteins that influence the whole closure, the development of predictive coupled chemo-mechanical models is still very scarce.

In this project we propose to develop computational tools that allow researchers to numerically simulate the biomechanical processes that drive wound closure. Due to the different behaviour at the interior and at the cell boundary, and the localisation of stress fibers at different depths, we will develop a three-dimensional model that explicitly represents the inter- and intra-cellular forces using a hybrid cell-centred/vertex approach.

This proposed model will simulate the relevant mechanisms such as tissue reorganisation, non-linear cell rheology (solid-like at short time, and fluid-like at long term), contractility increase, and the regulation of closure through ion and actin flow. We aim to analyse recent experimental observations, where wound closure is initiated by tissue crawling and thinning, which is eventually compensated by cell growth. The project will allow us to determine the influence of the flow of ions such as Ca2+, and analyse whether the latter migration-growth mechanism is energetically more favourable than the wound closure at a constant height, that is, than the growth-migration mechanism. The numerical results will be validated and compared with experimental measurements of the wound expansion, motility velocity, and time/spatial evolution of tissue thickness.

Wound closure is a vital process guaranteeing epithelial functionality, that is, to protect the organism and the organs, and control the correct proteinic exchange with the environment. However, the simulated mechanisms are not exclusive of the healing process, since they also appear in cell motility, during embryo development or in cell regeneration. For this reason, the design and implementation of computational tools that allow us simulating the underlying regulation in wound healing is also very relevant for understanding migration of cancer cells or regenerative medicine.