BRIGE: Active micro-rheology with spherical micro-confinement: A model for intracellular transport

Cornell University, Ithaca NY

Investigators

Abstract

Technical Description: The goal of this BRIGE proposal is to build a research and education program to discover and develop predictive theory for the active and passive transport of particles inside 3D-microscopically confined and concentrated complex fluids, with a view toward a model of intracellular transport inside eukaryotic cells. The interior of a eukaryotic cell is an active, crowded aqueous compartment that is populated by a multitude of nano-scale particles. Emerging studies suggest that much cellular function--e.g. metabolism, pattern formation, and cargo transport--is affected by simple physical transport, including diffusion and active towing by motor proteins. Several important open questions must be answered to understand how such motion affects cell function: What is the origin of anomalous diffusive behavior of particles in the cytoplasm? Does gradient diffusion or cytoplasmic streaming (or both) enable particle migration during pattern formation, division, and growth? What are the effects of micro-confinement? Recent models attempting to answer these questions assume a quiescent and unbound fluid, but the cytoplasmic fluid undergoes bulk advection due to its entrainment by self-propelled motor proteins, and even 1D confinement dramatically alters transport behavior. To approach this problem, the PI will construct a 3D simulation model utilizing the framework of Stokesian Dynamics, the premier technique for accurate modeling of particle-laden fluids. Prior to utilizing the simulation, however, theoretical work is required to develop the so-called mobility tensors?hydrodynamical "rules" for the way particles interact with each other and with an enclosure?and similar functions for representing the motion of self-propelled motor proteins. Equilibrium, gradient diffusion, and imposed flows that mirror motion inside a cell will be studied. The statistical distribution of particles, diffusion coefficients, effective viscosity, and stress will be computed. The simulation results will be compared to our theory that connects stress gradients to particle migration, and to experimental results. The intellectual merit of such understanding is high: the rheological behavior of fully 3D-confined suspensions is a largely unexplored area and thus constitutes a substantive and novel contribution to the rheology field. This knowledge will advance our understanding of the effects of finite domains on the rate at which energy is dissipated in Brownian systems. Broader Significance and Importance: The knowledge developed will create greater understanding of the dynamical fluid environment and transport inside the cell, will advance our understanding of how such processes are related to disease, and will facilitate the development of therapeutic tools. It will uniquely broaden connections between cell biology, engineering, and statistical physics by creating a novel first-principles model that can be built upon by any of these fields. Broadening Participation of Underrepresented Groups in Engineering: To broaden participation in STEM fields by under-represented minority students and to reach out to the general public, we will work to improve the interest, participation, and skills of such students in science by teaching critical skills: using the scientific method; identifying physical processes to predict behavior; and connecting mathematics to physical problems. To achieve this goal, the PI will develop interactive demonstrations and disseminate them via (1) Cornell classes; (2) Cornell outreach programs; and (3)quarterly "Science Scrimmage Days" at a National Academy Foundation high school for underrepresented minority students. This research has been funded through the Broadening Participation Research Initiation Grants in Engineering solicitation, which is part of the Broadening Participation in Engineering Program of the Engineering Education and Centers Division.