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

许多类型的细胞表现出不同的运动状态，由突起的动力学特征来区分。细胞运动受限于一维纤维连接蛋白通道，可能的突起形成方向的连续体限制在两个离散的前部和后部突起。然而，一维通道上的细胞运动出人意料地丰富着动态现象，显示出稳定和振荡的运动状态，以及静止状态和它们之间的转换。近年来，细胞的多重稳定性引起了人们对细胞作为动力系统的兴趣的激增。本课题采用实验和理论相结合的方法对多稳定性机理进行了研究。自动化时间推移显微镜和图像分析将用于生成关于微图案车道上的MDA-MB-231细胞轨迹和形态动力学的大型数据集。我们将在以前工作的基础上开发一个细胞运动性的生物物理模型，解释多个细胞状态的存在、它们的动力学性质以及状态之间的转换。我们将比较模拟和测量的形态动力学特征，即细胞速度、前后速度、细胞振荡的周期和幅度，作为黏附强度的函数，以及通过黏附强度和药物定义的扰动。该项目的目标是形成机械的想法，以提供对细胞作为动力系统的行为的洞察。特别是，我们将探索状态转变作为对粘合强度步骤的响应。沿着这条路线，细胞运动中的一般关系，特别是粘着-速度关系和UCSP，将从力学上得到澄清。

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.