Modeling ATP-mediated endothelial cell elongation on line patterns

The migration of endothelial cells (ECs) is critical for various processes including vascular wound healing, tumor angiogenesis, and the development of viable endovascular implants. Recent observations (time-lapse imaging over 12hr periods) in our laboratory of ECs cultured on line patterns - surfaces where cellular adhesion is limited to 15 ?m wide lines - have demonstrated the presence of three distinct migration phenotypes: a) running - cells are polarized and migrate continuously and persistently on the adhesive lines with possible directional changes, b) undecided - cells are elongated and exhibit periodic changes in the direction of their polarization and minimal net migration, and c) tumbling-like - cells migrate persistently for a certain amount of time but then stop and round up for a few hours before spreading again and resuming migration. Because EC migration is regulated by intracellular ATP levels and cellular elongation induced ATP release, we hypothesize that the three migration phenotypes on line patterns, which translate into different cell length variations in time, are related to different intracellular ATP profiles. Thus, we have developed a mathematical model to provide a description of the complex interactions between cell length, cytoskeletal (F-actin) organization, and intracellular ATP concentration. To identify the parameters that reproduce the experimental observations, we have implemented an optimization procedure that yields the parameter values that best fit the experimental data on cell lengths. The results show that depending on the parameter values adopted for the simulations, the different ATP profiles can indeed be obtained. Future work will focus on providing experimental evidence for the involvement of intracellular ATP in determining the three types of migration behavior.