Project 3 - Motility

趋化过程的最后阶段导致细胞的实际移动。这种运动涉及一系列复杂的细胞过程，包括产生伸展力、收缩力和粘附力。对这些力量的基本机制知之甚少，部分原因是缺乏定量数据。例如，目前尚不清楚Dlctyostellum细胞如何粘附到基底上，以及基底的硬度和刚度如何影响细胞运动性。然而，新的实验技术开辟了检查细胞迁移中所涉及的力的可能性，并可以为更深入地了解细胞运动提供必要的定量数据。我们在这个项目中的目标是双重的：第一个目标是确定在基板-细胞界面的力量和它们在细胞运动中的作用，使用新的微流体技术结合创新的基板，允许同时馏分显微镜和全内反射荧光（TIRF）显微镜。第二个目标是利用这些实验数据建立一个全面的细胞运动计算模型，包括力的产生，细胞-基质相互作用，膜特性和细胞变形。与项目1和项目2一样，实验-计算交互对实现我们的目标至关重要。具体而言，我们建议：

The final phase of the chemotactic process results in the actual movement of the cell. This movement involves a complex set of cellular processes and includes the generation of protrusive, retractive, and adhesive forces. The mechanisms underlying these forces are poorly understood, partially due to the lack of quantitative data. For example, it is unclear how Dlctyostellum cells adhere to the substrate, and how the substrate adhesiveness and rigidity affect cell motility. New experimental techniques, however, open up the possibility of examining the forces involved in cell migration and can provide quantitative data necessary for a deeper understanding of cell motility. Our goal in this project is two-fold: the first goal is to determine the forces at the substrate-cell interface and their role in cell motility using novel microfluidics techniques in combination with innovative substrates that allow for simultaneous fraction microscopy and Total Internal Reflection Fluorescence (TIRF) microscopy. The second goal is to use this experimental data to build a comprehensive computational model for cell motility that includes force generation, cell-substrate interactions, membrane properties and cell deformations. As in project 1 and 2, the experimental-computational interaction will be critical to achieving our goals. Specifically, we propose: