In silico phase-field modeling of cell directed migration towards environments of lower or higher adhesion

This work focuses on modeling adhesive haptotaxis in cell migration. While cells typically move toward regions of high adhesiveness, experiments on lymphocytes at the Laboratory of Adhesion & Inflammation (LAI) in Marseille have revealed an opposite behavior known as reverse adhesive hap-totaxis. To investigate this phenomenon, we adapt a single-cell migration model originally proposed by Aronson and Ziebert [Soft Matter 10 (2014) 1365-1373, PLoS One 8 (2013) 1-14, J. Roy. Soc. Interface 9 (2012) 1084-1092], which accounts for the dynamics of adhesion site density. In our adaptation, we exclude contractility and rear adhesion—factors likely irrelevant for lymphocyte propulsion [Aoun et al., Biophys. J. 119 (2020) 1157-1177] - and explore the role of adhesion signaling in two key processes: (i) propulsion at the cell front, as previously proposed in Ziebert and Aranson [PLoS One 8 (2013) 1-14], and (ii) actin polymerization within the cell, a novel aspect of this study. By thoroughly analyzing the interplay between these mechanisms, we demonstrate that our model can capture both classical and reverse haptotaxis. Notably, reverse haptotaxis emerges in this context when propulsion is coupled with positive feedback signaling mechanism but also when actin polymerization is coupled with negative feedback mechanism, suggesting the need for future experimental efforts to identify the corresponding signaling cascade in lymphocytes.