Nanoparticle Transport in Dynamically Deforming Extracellular Matrix Mimics under Cyclic Shear

In living tissues such as muscles, lungs, and blood vessels, the extracellular matrix (ECM) is not a static scaffold but undergoes periodic deformations due to physiological processes like breathing, heartbeat, and locomotion. Widely used as drug carriers, nanoparticles (NPs) are hypothesized to transport within such dynamically deforming matrices in a highly nontrivial way. Cyclic shear can result in temporal modulation of the pore size and network permeability of the ECM, thereby altering nanoparticle diffusion dynamics. In static hydrogels, NP motion departs from classical Brownian diffusion and is instead characterized by intermittent hopping between adjacent pores within the network. Despite extensive research on NP diffusion in static matrices, the role of cyclic deformation in regulating transport remains largely unexplored. In this study, we experimentally investigate the transport of NPs within an agarose hydrogel, a model ECM, subjected to controlled cyclic shear. The cyclic deformation was generated by an oscillatory flow in a custom-built channel, which imposed sinusoidal shear deformation on the hydrogel sample in the frequency range of 0.1–2 Hz. Fluorescently labeled nanoparticles embedded in the hydrogel were tracked using fluorescence microscopy. We systematically explore how the frequency and amplitude of shear deformation affect NP mobility and effective diffusivity within the gel matrix. Our findings elucidate the critical role of dynamic mechanical environments in governing nanoscale diffusion. This study provides valuable insights into the design of mechanically responsive therapeutic systems for enhancing drug delivery efficacy and minimizing off-target effects.