ArticleEuropean biophysics journal : EBJ2026
Simulation of intracellular delivery through permeabilized multivesicular vesicles.
Article in European biophysics journal : EBJ, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Cell permeabilization techniques are widely used to enable intracellular delivery of therapeutic molecules. Although these methods show promise for drug delivery and gene therapy, controlling and quantifying molecular transport at the nanoscale remains a significant challenge due to the structural complexity of mammalian cells. Multivesicular vesicles (MVVs), consisting of a large outer vesicle encapsulating multiple smaller vesicles, offer a simplified biomimetic platform that captures key aspects of cellular compartmentalization of mammalian cells. In this study, we employed finite element method (FEM)-based simulations using COMSOL Multiphysics to investigate passive molecular transport through permeabilized MVVs. The model incorporated biologically relevant pore sizes and three commonly used fluorescent probes of increasing molecular size: Calcein, Texas-red dextran 3000 (TRD-3k), and TRD-10k. The results reveal size-dependent accumulation kinetics. Additionally, transport efficiency was enhanced with increased pore diameter, indicating that both molecular and structural parameters influence delivery outcomes. Importantly, the simulations demonstrate that compartmentalized vesicle structures cause transport to vary across space and time. The model successfully matches experimental results seen in permeabilized vesicles and expands them to more complex nested vesicle systems. These findings highlight the role of vesicle architecture in shaping transport outcomes and provide a computational framework for exploring compartmentalization effects relevant to intracellular delivery strategies.
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