Understanding How Motile Cells Make Decisions When Subject to Multiple Chemical and Physical Cues

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Cells make behavioral decisions based on measurements of their environment all the time. Chemical cues re-orient cells towards food or sites of infection. Physical cues report on local hydrostatic pressure, cellular crowding, adhesion etc. Together these cues allow a cell to make decisions about its fate (if it is in an embryonic state), move, divide, assemble into a tissue etc. Understanding how cells integrate multiple physico-chemical measurements before making a decision is thus critical in characterizing tissue and organ development, wound healing, cancer metastasis and in controlling cells to create artificial tissues and organs. This award supports research that will combine experimental and theoretical studies to study how a single cell can integrate physical and chemical cues to decide which direction to move in. Since all natural and artificial tissues contain cells, understanding how they make decisions will allow for better control of natural tissues and provide guidelines for creating artificial functional tissues. Thus this research will help society. Furthermore, as the research is highly multi-disciplinary and involves tools and techniques from molecular biology, microscopy, microfluidics on the one hand, and statistical and nonlinear physics, hydrodynamics, and optimization and control theory on the other, it will broaden participation of engineers and scientists from many different group including under-represented minorities and positively impact engineering education by fertilizing different disciplines.Oriented motility of cells in response to external cues is critical in determining the survival of single-celled organisms and the normal development and maintenance of multi-cellular organisms like us. The molecular basis for this orientation has been widely studied but an integrated quantitative model remains elusive, in part due to the absence of controlled quantitative environments. This award will support research to close the gap. Microenvironments that can be programmed with both chemical and physical cues will force neutrophils to crawl through channels they occlude and provide high-resolution images of intracellular signaling for automated data analysis. The ability to quantitatively control the cellular environment and simultaneously measure intracellular signaling will allow for a multi-phase model of cell polarization and motility that accounts for cytoskeletal and membrane dynamics combining statistical mechanics, hydrodynamics and elasticity, while integrating the sensing of the physical (pressure) and chemical (cytokine) environment into a biophysical basis for cellular decision making.