Multistability and protrusion competition of motile cells on micro-patterned lanes: a biophysical approach to cell motility

点击翻译按钮获取中文摘要

Many cell types exhibit a variety of motile states distinguished by the dynamics of protrusions. Confinement of cell motility to one-dimensional Fibronectin lanes restricts the continuum of directions of possible protrusion formation to two discrete front and rear protrusions. Yet, cell motion on one-dimensional lanes is surprisingly rich in dynamic phenomena showing steady and oscillatory moving states as well as resting states and transitions between them. The observed multistability caused a surge of interest in cells as dynamical systems in recent years. The present project investigates mechanisms of multistability combining experiment and theory. Automized time-lapse microscopy and image analysis will be used to generate large data sets of MDA-MB-231 cell trajectories and morphodynamics on micro-patterned lanes. We will develop a biophysical model of cell motility based on our previous work explaining the existence of multiple cell states, their dynamic properties and transitions between states. We will compare simulated and measured morphodynamic features, i.e. cell speed, front and rear velocities, and periods and amplitudes of cell oscillations, as a function of adhesion strength and defined perturbations by adhesion strength and drugs. The goal of the project is to formulate mechanistic ideas that provide insights into cell behavior as dynamical systems. In particular, we will probe state transitions as response to steps in adhesion strength. Following this route, general relations in cell motility, notably the adhesion-velocity relation and UCSP, will be mechanistically clarified.