469800 A Molecular Thermodynamic Model for Nanoparticle-Membrane Interactions
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.