Cells actively change their shape during essential life processes, from cell division to migration. Their ability to do so depends upon their mechanical properties and their ability to generate mechanical forces, which are mediated by the internal scaffolding of the cell (cytoskeleton). Far from a static structure, the cytoskeleton is highly dynamic, as it is constantly assembled and disassembled, yet maintains the shape of the cell continuously. Without precedent in modern engineering, little is known regarding how the internal dynamics of assembly and disassembly within this material impacts the mechanical properties of the material itself. Nor is it understood how cells use this relationship to generate forces and change its shape, as occurs throughout its lifetime. To explore these relationships, the research team will engineer simplified, non-living versions of cells where the internal dynamics of the cytoskeleton can be controlled precisely and its impact on mechanics and "cell" shape can be measured quantitatively. In parallel, they will use computational simulation to uncover how the modulation of internal dynamics manifests in mechanical changes of the cytoskeleton, providing insight into the development of new biologically-inspired materials.
The F-actin cytoskeleton provides the structural and mechanical support that maintains cell shape and mediates force production during essential life processes including cell division and migration. The F-actin cytoskeleton is also highly dynamic, constantly assembling and disassembling, renewing itself in minutes. However, how the renewal of the F-actin cytoskeleton (turnover) impacts the time-dependent mechanical properties of the cell, and its capacity to generate mechanical forces is uncertain. Also uncertain, is how these mechanical changes in the F-actin cytoskeleton regulate the dynamics of cell shape change. Connecting the dynamics of F-actin turnover to the mechanical behaviors of the cell has been difficult because the biochemical factors that control turnover are regulated internally through complex and overlapping pathways. To reduce this complexity, the research team plans to reproduce shape changes within simplified, biomimetic cells in vitro, engineered from purified proteins and lipids, whose biochemical composition is controlled precisely. With this "bottom-up" approach, the complicating influence of biochemical and genetic regulation by living cells is eliminated, facilitating the determination of a quantitative relationship between F-actin turnover, and the resultant mechanical and morphological changes in the "cell". In parallel, they plan to conduct computational simulations to determine the molecular mechanisms by which the kinetics of F-actin turnover influence cytoskeletal mechanics, force production, and the experimentally observed changes in cell shape.
