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Critical to many physiological and pathological processes, human cells exhibit motility responses to a variety of chemical and mechanical environmental factors. This includes both contact guidance, where cells migrate along the ECM fibers, and chemotaxis, in which cells move toward chemoattractant. Independently both cases had been studied extensively. However, there are some synergistic effects that are not fully characterized in 3D cell migration. To reveal the combined effects of mechanical and chemical guidance, and quantitatively analyze the strength of the crosstalk of these two driving cues, we develop a microfluidics device to control the strength of chemoattractant gradient as well as contact guidance cues by aligning surrounding ECM fibers of each individual cell. In addition, to objectively characterize the cell migration and morphologies, we developed a machine-learning-based cell tracking method. This novel experimental platform enabled us to observe how cells respond to chemotaxis and contact guidance cues in three major categories.
In the first category, when mechanical and chemical cues are perpendicular, we observed two types of behavior. About one-third of the cells follow a strong chemotaxis effect through a “hopping effect” meaning cells hop from an ECM fiber to the neighboring ECM fiber with overall cell migration toward chemoattractant on average speed. The rest of the cells in this category strongly follow the ECM fibers with about the same speed as the other ones and ignore the chemotaxis effect.For the second category, the ECM fibers are parallel with the chemo-attractant gradient vector. Under this condition, the overall migration speed is larger but the “hopping effect” is much weaker in comparison with the first category while the overall chemotaxis effect is the same. In our continuing work, we will develop a mathematical model to recapitulate our experimental observations and fully characterize the cell response to coupled chemical and mechanical cues.
Biography: Pedram Esfahani is a graduate student in Physics at OSU, working with Bo Sun.