(455b) Cytoplasmic Flow and Dispersion in Deforming Cells

The cytoplasm of a living cell is a complex, dynamic physical environment through which the molecular components essential to cell function must move. Bulk fluid flow of this medium can couple whole cell deformation to the transport and dispersion of intracellular particles. Large deformations are especially evident in motile cells such as human neutrophils, which can crawl through two- and three-dimensional environments while undergoing significant morphological changes. Motivated by the complex motion of intracellular components within these cells, we explore the coupling between deformation, flow, and transport in a simplified physical model.

We study the general problem of mixing and dispersion within a fluctuating membrane-enclosed fluid domain. Using spectral analytic methods, we demonstrate that thermal fluctuations of the membrane result in time-dependent hydrodynamic correlations between enclosed particles, which can affect multi-particle interactions on or near the membrane. We also consider active forcing of the membrane, reminiscent of the protrusion forces generated by actin polymerization during cell motility. We quantify the Taylor dispersion of particles within a quasi-spherical deforming domain, arising from a combination of particle diffusion and advection by the fluid flows associated with deformation. The effect of this dispersion on overall mixing of particles throughout the cell is explored, and an significant acceleration (up to a factor of 2) is demonstrated in particle encounter rates, implying a global impact of dynamic cell deformation on transport kinetics within the cytoplasm.

We further use phase contrast video microscopy to record the morphological dynamics of neutrophils crawling in a two-dimensional environment, and fluorescence microscopy to track the motion of organelles within the cytoplasm. We find qualitative agreement between the dispersion of these intracellular particles and our simplified model of a dynamically deforming membrane-enclosed domain. Namely, the organelle motion on second to minute timescales is found to be dominated by cytoplasmic flows associated with cell deformation.

Our findings demonstrate a role for cytoplasmic fluid flow induced by large-scale cell deformation on the transport and dispersion of intracellular components.