388418 Cytoplasmic Fluid Flow and Intracellular Transport in Motile Cells
The cytoplasm of a living cell forms a dynamic, complex physical environment wherein active and passive molecular processes act in concert to fulfill the biological needs of the cell. This global mechanical environment can couple local perturbations to large-scale modification of intracellular transport and reaction rates. The impact of mechanics and rheology on the cell's biological function remains poorly understood and is an area of active research.
We study the mechanical properties of motile animal cells, with a focus on human neutrophils. These cells exhibit rapid motion accompanied by significant dynamic changes in cell shape. The large-scale movement of the cell boundary is expected, in turn, to impact the motion of intracellular components. We develop a minimalist model of the cytoplasm as an effective viscous fluid. Using phase contrast and fluorescent microscopy to track the cell boundary motion, we solve for the concomitant fluid flow within the cell.
This simple model allows us to couple the boundary motion of the cell with the motion of its interior, without any fitted parameters. We demonstrate that the fluid flows expected to arise from cell motility dominate over diffusion for particles on the size scale of large protein complexes and organelles. Furthermore, we use fluorescent tracking of large intracellular particles to compare their relative motion with the predictions of the fluid model.
The specific biological system of crawling neutrophils motivates the study of a more general physical problem: the motion of a particle near an actively fluctuating membrane. We use a combination of analytical theory and computation to investigate the fluid mixing which arises from correlated random forces applied to an elastic membrane and the role of the resulting fluid flows on transport properties in the proximal medium.
Our findings demonstrate that fluid flows in the cytoplasm can couple active processes at the cell boundary with mixing of the cell interior, yielding a nontrivial effect on the transport of intracellular components.