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.
