Hydrodynamic dispersion drives viral-cellular contact for gene delivery in porous media
Srikanth, V.; Mallory, M.; Ulmer, A. J.; Legant, W. R.; Kuznetsov, A. V.; Brudno, Y.
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Reactive biological processes often hinge on rare collisions between particles that occupy vastly different physical regimes, yet the transport physics that govern these encounters remain poorly understood. 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 through slow Brownian diffusion, while microscale cells rapidly sediment, producing species separation that suppresses the virus-cell interaction interface. 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.
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