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Biology subjects

Brudno, Y.

Publications and source records attributed to Brudno, Y..

2 recordsLinked to original sources

Hydrodynamic dispersion drives viral-cellular contact for gene delivery in porous media

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.

bioengineering↗

Optimizing canine T cell activation, expansion, and transduction

Dogs are becoming an important model for human cancers, and successfully troubleshooting issues with genetically modified T cell immunotherapy for round cell and solid neoplasms in dogs provides a unique opportunity to improve efficacy, safety, and affordability for humans as well. Unfortunately, T cell activation in dogs for optimal viral transduction has not been determined, restricting advancements in canine T cell immunotherapy. Two CD3 and two CD28 antibody clones for canine T cell stimulation have been described in the literature, but no studies have been undertaken to evaluate which CD3/CD28 combination is most effective, nor has anyone directly compared the efficacy of the two most popular antibody presentation strategies: antibody-coated plates and antibody-conjugated beads. In evaluating the effects of plate- or bead-bound CD3 stimulation alone versus CD3/CD28 in combination, we tested 12 possible antibody stimulation strategies in addition to evaluating two largely unexplored mitogens in canine T cell transduction, phorbol myristate acetate (PMA) with ionomycin and concanavalin A (ConA). We investigated the impact of these stimulation strategies on canine T cell activation, expansion, and transduction. For stimulation strategies producing the best results, we also examined how each strategy affected the proportions of CD4/CD8 T cell subsets and regulatory T cell (Treg) prevalence. We determined that, in general, plate-bound antibodies were far superior to bead-bound antibodies for canine T cell stimulation, and that plate-bound CD3 clone CA17.6F9 in combination with CD28 clone 5B8 or the mitogen PMA with ionomycin produced better activation and expansion profiles, better transduction, and more desirable T cell subsets that are more likely to improve patient outcomes in dogs suffering from round cell and solid tumors.

immunology↗