(584g) Understanding Particle-Cell Interactions Under Shear

Interactions of nano- and micron-sized particles with cell membranes underpins many modern biomedical processes, particularly in drug delivery and cell therapies. Ensuring optimal pharmacokinetics and cellular uptake in nanomedicine requires precise engineering of the nanoparticle size, shape, and surface chemistry depending on the cell-specific membrane mechanics of interest. More importantly, they need to account for the physiological flow environment, such as the blood circulation. The influences of particle properties on their cell interactions are often non-monotonic, interdependent and competitive. Accurate physical modelling based on a quantitative understanding of particle-membrane interactions can reduce reliance on brute-force experimental approaches to tailor-made particles. However, resolving the influence of nanoparticles is computationally expensive using existing cell-level simulations.

We previously developed a model for particle-membrane interactions in the absence of fluid flow at finite particle concentrations. Here we present our new findings accounting for flow conditions that influence both membrane deformation and the adhesive interaction between nanoparticles and the cell membrane. We aim to determine the threshold of particle detachment as a function of various particle parameters and flow environment in vivo and in vitro. Findings from this study will be beneficial for a multi-scaling modeling approach with reduced computational costs. Therefore, our results bridge the knowledge gap between predictive models based on fundamental particle-cell interaction mechanisms and tailor-made nanoscale material designs.