Modeling ATP-mediated endothelial cell elongation on line patterns

Abstract

Endothelial cell (EC) migration is crucial for a wide range of processes including vascular wound healing, tumor angiogenesis, and the development of viable endovascular implants. We have previously demonstrated that ECs cultured on 15-μm wide adhesive line patterns exhibit three distinct migration phenotypes: (a) “running” cells that are polarized and migrate continuously and persistently on the adhesive lines with possible spontaneous directional changes, (b) “undecided” cells that are highly elongated and exhibit periodic changes in the direction of their polarization while maintaining minimal net migration, and (c) “tumbling-like” cells that migrate persistently for a certain amount of time but then stop and round up for a few hours before spreading again and resuming migration. Importantly, the three migration patterns are associated with distinct profiles of cell length. Because of the impact of adenosine triphosphate (ATP) on cytoskeletal organization and cell polarization, we hypothesize that the observed differences in EC length among the three different migration phenotypes are driven by differences in intracellular ATP levels. In the present work, we develop a mathematical model that incorporates the interactions between cell length, cytoskeletal (F-actin) organization, and intracellular ATP concentration. An optimization procedure is used to obtain the model parameter values that best fit the experimental data on EC lengths. The results indicate that a minimalist model based on differences in intracellular ATP levels is capable of capturing the different cell length profiles observed experimentally.