Using Finite Element Modeling to Gain Insights into the Mechanics of Wound Healing in Drosophila

Abstract

Although it is not difficult to observe the healing of induced wounds in animal embryos, mapping the forces that drive lesion closure has proved challenging. Laser microsurgery, Atomic Force Microscopy (AFM) and other techniques can provide local information at fixed times, but all are invasive and some disrupt further development. Video Force Microscopy (VFM) has been able to map driving forces during ventral furrow formation in Drosophila (fruit fly), but challenges arose when it was applied under the assumption that the only driving forces are intracellular pressures and forces (including purse string action) along cell edges. Other possible forces of relevance include far-field stresses and in-plane cellular contractions. Mapping the forces that drive wound closure is an important problem, and so far it has remained unsolved.

To investigate the process of dorsal closure, this study used a cell-based finite element (FE) model to identify the mechanical signatures of a wide variety of possible driving forces. Geometric parameters were developed to characterize the associated cell shapes and tissue motions and to quantitatively compare FE simulations with each other and with experimental data. It was discovered that edge tensions and pressures were not sufficient to drive wound healing. Wound healing can only be achieved when far-field boundary motions, edge tensions and apical area tensions act together.

This thesis shows that a suitable FE model can provide information about the forces that drive wound healing, and its simulations take us one step closer to understanding the mechanics of wound healing. It also contributes to our general understanding of the forces that drive morphogenetic movements and ultimately helps us to better understand cell-based processes important for human quality of life.