(717d) A Molecular Thermodynamic Model for Nanoparticle-Membrane Interactions

The thermodynamics of nanoparticle interactions with cellular membranes has momentous consequences for nanotechnology with biological, toxicological, and pharmacological applications. The pervasiveness of nanoparticles in therapeutics, foods and beverages, cooking products, packaging, cosmetics and sunscreens, and agriculture, amongst many other areas, coupled with the lack of fundamental understanding of the interplay of particle design effects like size, chemistry, shape, and elasticity on product performance, underscores the importance of a biophysical approach to nanoparticle-membrane interactions. Here, we use molecular dynamics simulations to characterize the behavior of homogeneous, spherical nanoparticles with model lipid bilayers. We delineate unique mechanistic modes of particle-membrane interaction in the space of nanoparticle size and chemistry (hydrophobic/philic). We uncover a diverse array of stable and long-lived metastable configurations that vary sensitively with the effective particle attractions to lipid head and tail groups, and with size as particles move from the molecular (<0.5 nm) to lower â??colloidalâ? (>10 nm) regime.

Continuum theory provides a starting point for understanding some of these behaviors, particularly at the extremes of small molecules (solubility theory) and large colloidal particles (membrane elastic theory). The intermediate nanoscale regime, however, is complex because the membrane thickness (~5 nm) is comparable to the particle size, individual lipid fluctuations become relevant, and significant geometric asymmetries of inserted configurations emerge. We implement the molecular simulations to direct the development of new theory in this regime. We use calculated lipid leaflet distributions and field-based descriptors of membranes with inserted particles to extend existing theoretical models with free energetic contributions from deformations in lipid molecular tilt, twist, and splay. We then investigate improvements in these continuum predictions through comparison with detailed umbrella sampling free energy calculations. While focused on model systems, this nanoparticle study has interesting implications for a wide range of organic and inorganic nanoparticles, and also for biomacromolecules like membrane proteins.