Abstract
ABSTRACTDespite recent experimental progress characterizing the mechanics of cell migration, our understanding of the mechanisms governing how cells move rapidly through the body remains limited. To effectively limit the growth of tumors, antitumoral T cells need to rapidly migrate to find and kill cancer cells. To understand what sets the upper limit on cell speed, we developed a new hybrid stochastic-mean field model of bleb-based cell motility to guide T cell engineering approaches to enhance T cell movement in tumor environments. We first examined the potential for adhesion-free bleb-based migration and show that cells only inefficiently migrate in the absence of adhesion-based forces, i.e., cell swimming. High-to-low cortical contractility oscillations, where a high cortical contractility phase characterized by multiple bleb nucleation events is followed by an intracellular pressure buildup recovery phase at low cortical tensions, results in modest net cell motion. However, our model suggests that cells can employ a hybrid bleb- and adhesion-based migration mechanism for rapid cell motility and identifies conditions for optimality. The model provides a momentum-conserving mechanism underlying rapid single-cell migration and identifies factors that can be used as design criteria for engineering T cell therapies that move better in mechanically complex environments.
Publisher
Cold Spring Harbor Laboratory