Modeling Interactions between Multicomponent Vesicles and Antimicrobial Peptide-Inspired Nanoparticles

We examine the interaction between peptide inspired nanoparticles, or nanopins, and multicomponent vesicles using the dissipative particle dynamics simulation technique. We study the role of nanopin architecture and cholesterol concentration on the binding of the nanopins to the lipid bilayer, their insertion, and postembedding self-organization. We find the insertion to be triggered by enthalpically unfavorable interactions between the hydrophilic solvent and the lipophilic components of the nanopins. The nanopins are observed to form aggregates in solution, insert into the bilayer, and disassemble into the individual nanopins following the insertion process. We examine factors that influence the orientation of the nanopins in the host vesicle. We report the length of the hydrophilic segment of the nanopins to regulate their orientation within the clusters before the embedding process and in the bilayer, after the postinsertion disassembly of the aggregates. The orientation angle distribution for a given nanopin architecture is found to be driven by energy minimization. In addition, higher concentration of cholesterol is observed to constrain the orientation of the nanopins. We also report thermal fluctuations to induce transverse diffusion of nanopins with specific architectures. The incidence of transverse diffusion is observed to decrease with the concentration of cholesterol. Our results can provide guidelines for designing peptide inspired nanoparticles or macromolecules that can interface with living cells to serve as sensors for applications in medicine, sustainability, and energy.