Integration of topographical, mechanical and biochemical signals in cell motility

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In this proposal the PIs will investigate how highly motile cells such as the model organism Dictyostelium discoideum determine its forward direction of motion. The PIs will investigate this question taking into account all information about their surrounding and will integrate signals of different type - surface topography, mechanical force exerted by their surrounding as well as biochemical signals. The PIs will focus on the study of topography, mechanical and biochemical signals together in the same cell. Their goal is to develop quantitative experiments amenable to comparison to simple, tractable models for the coupling between the mechanical and biochemical pathways of the cell. They will apply small local perturbations to both biochemical and mechanical pathways using functionalized beads held by holographic laser tweezers, and measure both putative upstream and downstream responses of the cell. In addition, they will fabricate surfaces of controlled topography to generate large scale perturbations. The measured cell response will be compared with simulations of reaction diffusion based model systems of the key signaling molecules exposed to similar perturbations. Such perturbation analysis is sensitive to the structure of the signaling pathways, and will allow the validation of the coupled topographical, mechanical and biochemical pathways. This work will train quantitative scientists for interdisciplinary work at the interface of physics and biology. As part of this project the PIs will develop demonstration materials on cell motility. These demos will be used in undergraduate courses, university open houses, and public lectures. Undergraduate students will be involved in the proposed research. The PIs will actively recruit and aid in retention of underrepresented minorities through mentoring of local high school students, lab tours, and programs supported by the College of Math and Physical Sciences. The understanding of the integration of the mechanical and biochemical signals will help in designing better drugs and new approaches to control cell differentiation, tissue formation, organ development, or other processes where biochemical and mechanical signals are tightly coupled.