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Transient Expression of Proteins by Hydrodynamic Gene Delivery in Mice
Published on: May 5, 2014
Hydrodynamic dispersion drives viral-cellular contact for gene delivery in porous media
Vishal Srikanth1, Micah Mallory2, Andrew J Ulmer2
1Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Abstract:
Reactive biological processes often hinge on rare collisions between particles whose transport is governed by disparate advective, diffusive, and sedimentary mechanisms. Biological cell-virus encounters offer a uniquely quantifiable instance of this general problem: collisions between particles whose transport is governed by entirely different physical mechanisms, yet whose interactions determine system-level function. In stagnant liquids, nanoscale viral vectors explore space only via slow Brownian diffusion, whereas microscale cells rapidly sediment, producing species separation that suppresses virus-cell interfacial interactions. Here we show that liquid absorption into a dry, macroporous sponge enhances viral-cellular interactions by shifting the system into an advection-dispersion regime that circumvents this sedimentation-diffusion limit. By integrating experimental results with a multiscale simulation model, we demonstrate that the tortuous sponge porosity converts capillary-driven flow into convective mixing, driving orders-of-magnitude increases in viral-cellular collision rates. Coupling these dispersive transport dynamics with a probabilistic capture model reveals that hydrodynamic dispersion accounts for the multifold enhancement in viral-cellular transduction efficiency observed in porous sponges. These results provide a quantitative framework for emergent collision dynamics in complex porous media and establish a generalizable strategy to optimize active transport in spatiotemporally heterogeneous biological systems.

