(469b) Nanoparticle Transport across Biomembranes: Probing the Limits and Consequences of Solubility-Diffusion Theories through Multiscale Modeling
AIChE Annual Meeting
Wednesday, October 31, 2018 - 8:15am to 8:30am
The interactions of nanoparticles (NPs) with cellular membranes and subsequent transport processes across them have major implications for the biology, toxicology, and pharmacology of nanoscale materials. While an understanding of the behaviors of diverse NP designs in a physiological setting is of increasing technological and regulatory importance, the current complexity of experiments and lack of consensus in modeling preclude a predictive framework for relevant NP-membrane interaction modes and mechanisms, particularly for particles on the ~1-10 nm scale. Here, we leverage detailed coarse-grained molecular dynamics simulations with advanced sampling strategies to uncover the thermodynamic driving forces and possible kinetic pathways of approximately 0.5-2.0 nm hydrophilic, hydrophobic, and âinterfacially activeâ particles with model lipid bilayer membranes. Using the simulations, we test the applicability of well-established theories for the permeability of small molecule transportâOvertonâs Rule and the inhomogeneous solubility-diffusion (ISD) modelâand conclude that the former is overly-simplified for fluctuating lipid bilayers, while the latter breaks down at the larger particle sizes due to the influence of other physics like membrane undulations. Where the mechanistic assumptions and quantitative predictions of the ISD model do apply, we construct structure-property correlations to obtain steady-state design rules for NP permeation and employ mass transfer & chemical kinetics to analyze transient effects. Where small-scale theories do not apply, we conclude with critical physical and methodological insights to guide future thermodynamic and kinetic studies of NP-membrane interactions.