Cell motility is an important physiological phenomenon attracting much attention in biology and medicine. It is based on a remarkable self-organized mechanochemical machine that consists of subcellular modules, such as (i) actin based protrusion, (ii) myosin powered contraction, (iii) graded adhesion, and (iv) membrane resistance. While molecular inventories of these modules are becoming available, understanding of the motile cell at the systems biology level is lacking. This understanding has to be achieved first for the simple shaped cells, such as fish epithelial keratocytes. The objective of this research is to use a novel combination of mathematical analysis, computer simulations and model-driven experiments to integrate the subcellular motility modules into a multi-scale computational model of the motile keratocyte cell. These tools will be used to find out whether there is a significant cytoplasmic flow in the cell affecting diffusive transport of molecules, what is the role of molecular motors and membrane in stability of stationary and motile cells, and what is the precise way of integrating subcellular motility modules determining motile cell shape.
There has been enormous interest in cell motility--ubiquitous phenomenon underlying wound healing, embryogenesis and cancer metastasis. Cells move by (i) extending protrusive appendages at the front, (ii) developing contractions inside, and (iii) forming firm adhesion to the surface at the front and weak at the rear. While molecular mechanisms of these three steps are becoming clear, understanding of the motile cell as a system is lacking. This project will provide systems-level understanding of the cell motility dynamics and result in predictive model of the crawling cell. The model will help to design experiments that will elucidate cell motile behavior in important physiological and medical systems. Students trained through involvement in this research project will become part of a new generation of interdisciplinary research force.
