Mechanistic Pathway of Lipid Phase-Dependent Lipid Corona Formation on Phenylalanine-Functionalized Gold Nanoparticles: A Combined Experimental and Molecular Dynamics Simulation Study.

In recent years, the underlying mechanism of formation of the lipid corona and its stability have begun to garner interest in the nanoscience community. However, until now, very little is known about the role of different properties of nanoparticles (NPs) (surface charge density, hydrophobicity, and size) in lipid corona formation. Apart from the physicochemical properties of NPs, the different properties of lipids remain elusive in lipid corona formation. In the present contribution, we have investigated the interaction of phenylalanine-functionalized gold NPs (Au-Phe NPs) with different zwitterionic lipid vesicles of different phase states (sol-gel and liquid crystalline at room temperature) as a function of lipid concentration. The main objective of the present work is to understand how the lipid phase affects lipid corona formation and lipid-induced aggregation in various media. Our results establish that the lipid phase state, area per lipid head group, and the buffer medium play important roles in lipid-induced aggregation. The lipid corona occurs for NPs at high lipid concentration, irrespective of the phase states and area per lipid head group of the lipid bilayer. Notably, the lipid corona also forms at a low concentration of lipid vesicles in the liquid crystalline phase (1,2-dioleoyl--glycero-3-phosphocholine). The corona formation brings in remarkable stability to NPs against freeze-thaw cycles. Based on the stability, for the first time, we classify lipid corona as "hard lipid corona" and "soft lipid corona". This distinct classification will help to develop suitable nanomaterials for various biomedical applications.