Simulation of phase behavior in lipid bilayers, vesicles, and wrapped nanoparticles
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Lipids, specifically phospholipids like dipalmitoylphosphatidylcholine (DPPC), undergo an order/disorder phase transition between fluid and gel states at ambient temperature and pressure. In the case of lipid-wrapped nanoparticles (LNP), where lipids are wrapped around a nanoparticle core, additional factors like curvature and nano-lipid interaction are present, resulting in a relatively poor understanding of the transition. Computer simulation, specifically molecular dynamics, is an ideal technique to study the fluid/gel transition from the molecular viewpoint. However, simulation of phase transitions is difficult; large free energy barriers separate stable phases, leading to broken ergodicity. Enhanced sampling methods are necessary to study rare events, like phase transitions, which occur on the second, or longer, timescale. Two such methods, the generalized replica exchange method (gREM) and statistical temperature molecular dynamics (STMD), and their recent developments, utilize generalized ensembles to provide enhanced sampling near phase transitions. Using the above methods,we studied flat lamellar bilayers, followed by more complex curved vesicles, and ultimately LNP. In bilayers, the gREM finds a strong coupling between phase transitions of the lipid and water subsystems. Subsequent simulations on an implicit water bilayer revealed distinct subphase transitions between coexisting states of fluid and gel lipids. STMD applied to vesicles shows weakening of the transition and overall lowering of the transition temperature with decreasing diameter, from first order at 40 nm to borderline first/second order at 20 nm and 10 nm. No homogeneous gel phase is formed, instead, low energy structures exhibit a faceted gel phase with gel patches separated by fluid lipid seams. For LNP, we find that curvature promotes the fluid phase but the presence of a core induces order, particularly in the inner layer. This nontrivial balance results in a broad, continuous phase transition for small LNP that becomes a sharp, first order transition between distinct fluid and gel states for large LNP. Overall, LNP hold great promise in a wide range of fields like drug delivery, imaging, and photocatalysis. We aim to provide a first-principles understanding of their properties by utilizing innovative simulation methods to obtain molecular details not available to experimental or traditional methods.