The Dynamics of Contracting Gels During Cell Crawling and Blebbing

在这个项目中，PI将专注于开发一个定量数学模型，描述细胞爬行过程中细胞骨架变形与细胞质流体流动耦合的物理现象，然后使用线虫精子作为模型系统对该模型进行测试。该项目由三部分组成。第一部分将使用线性、两相、稳态模型来描述解聚驱动的线虫精子运动，作为构建一个完整的非线性、移动边界模型的基础，该模型描述了这些爬行细胞中的力产生和流动。该模型将包括细胞膜对流体流动的渗透性，这在细胞运动模型中经常被忽略。该项目的第二个目的是做定量实验来检验模型的具体预测。使用DIC显微镜和Wolgemuth实验室开发的细胞跟踪算法，实验将探索秀丽隐杆线虫精子的速度如何取决于形状和底物粘附性。此外，荧光珠嵌入弹性衬底将用于测量由细胞产生的局部牵引力。粒子成像测速技术将用于测量细胞内的细胞骨架速度。第三个目标是测试最近提出的假设，即细胞泡胀（静水压力差驱动细胞质流体流动，使膜从细胞骨架上撕裂的过程）可能为爬行细胞的前缘提供了一些突出力。为了验证这一假设，PI将开发一种新的数学描述细胞边缘的细胞骨架和细胞质的行为。参与这项研究的学生将在理论和实验的界面上工作。这项研究的结果将通过在跨学科期刊上发表和在主要国际会议上发表报告的方式广泛传播。

In this project the PI will focus on developing a quantitative mathematical model that describes the physics of cytoskeletal deformation coupled to cytosolic fluid flow during cell crawling and then testing this model using nematode sperm as a model system. The project consists of three parts. The first part will use a linear, two-phase, steady state model for the depolymerization-driven motility of nematode sperm as a foundation for construction of a full nonlinear, moving boundary model that describes force generation and flow in these crawling cells. This model will include the permeability of the cell membrane to fluid flow, which is often neglected in models for cell motility. The second aim of the project is to do quantitative experiments to test specific predictions of the model. Using DIC microscopy and a cell tracking algorithm developed in the Wolgemuth lab, experiments will be done to explore how the speed of C. elegans sperm depends on shape and substrate adhesion. In addition, fluorescent beads embedded in elastic substrates will be used to measure the local traction forces generated by the cell. Particle Imaging Velocimetry techniques will be used to measure the cytoskeletal velocities inside the cell. The third aim will test the recently proposed hypothesis that cell blebbing (a process by which hydrostatic pressure differences drive the cytosolic fluid flow to rip the membrane away from the cytoskeleton) may provide some of the protrusive force at the leading edge of crawling cells. To test this hypothesis the PI will develop a new mathematical description of the behavior of the cytoskeleton and cytosol at the leading edge of the cell. Students involved in this research will work at the interface of theory and experiments. The results of this research will be broadly disseminated by publication in interdisciplinary journals and presentations at major international conferences.