Project Description

Computational models for wound healing

Principal Investigator: Jose J. Muñoz

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.