Cell motility is a fascinating dynamic process crucial for a wide variety of biological phenomena including defense against injury or infection, embryogenesis and cancer metastasis. A spatially extended, self-organized, mechanochemical machine consisting of numerous actin polymers, accessory proteins and molecular motors drives this process. This impressive assembly self-organizes over several orders of magnitude in both the temporal and spatial domains bridging from the fast dynamics of individual molecular-sized building blocks to the persistent motion of whole cells over minutes and hours. The molecular players involved in the process and the basic biochemical mechanisms are largely known. However, the principles governing the assembly of the motility apparatus, which involve an intricate interplay between biophysical processes and biochemical reactions, are still poorly understood. The proposed research is focused on investigating the biophysical aspects of the self-organization processes underlying cell motility and trying to adapt these processes to instill motility in artificial cells. Important biophysical characteristics of moving cells such as the intracellular fluid flow and membrane tension will be measured and their effect on the motility process will be examined, using fish epithelial keratocytes as a model system. The dynamics of the system will be further investigated by quantitatively analyzing the morphological and kinematic variation displayed by a population of cells and by an individual cell through time. Such measurements will feed into and direct the development of quantitative theoretical models. In parallel, I will work toward the development of a synthetic physical model system for cell motility by encapsulating the actin machinery in a cell-sized compartment. This synthetic system will allow cell motility to be studied in a simplified and controlled environment, detached from the complexity of the living cell.
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