The Dynamics of Contracting Gels During Cell Crawling and Blebbing

在本项目中，PI将专注于开发一种定量数学模型，该模型描述了细胞爬行期间细胞骨架变形与细胞溶质流动耦合的物理学，然后使用线虫精子作为模型系统测试该模型。该项目包括三个部分。第一部分将使用线性，两相，稳态模型解聚驱动的运动的线虫精子作为一个完整的非线性，移动边界模型，描述力的产生和流动，在这些爬行细胞的建设的基础。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。该项目的第二个目标是进行定量实验，以测试模型的具体预测。使用DIC显微镜和Wolgemuth实验室开发的细胞跟踪算法，将进行实验以探索C。精子的形状和基质的粘附性决定精子的大小。此外，嵌入弹性基底中的荧光珠将用于测量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。第三个目标将测试最近提出的假设，即细胞起泡（流体静压差驱动细胞溶质流体流动以将膜从细胞骨架撕裂的过程）可能在爬行细胞的前缘提供一些扩张力。为了验证这一假设，PI将开发一种新的数学描述的行为的细胞骨架和胞质溶胶在前沿的细胞。参与这项研究的学生将在理论和实验的接口工作。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.