Energy landscape for the insertion of amphiphilic nanoparticles into lipid membranes: A computational study
Name
journal.pone.0209492.pdf
Description
Published version
Size
2.32 MB
Format
Adobe PDF
Checksum (MD5)
3456793191b120156476850ff4a9e0a4
Author(s)
Van Lehn, Reid C
Alexander-Katz, Alfredo
Date Issued
2019
Journal
PLoS ONE
Publisher
Public Library of Science (PLoS)
Version
Final published version
Abstract
© 2019 Van Lehn, Alexander-Katz. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Amphiphilic, monolayer-protected gold nanoparticles (NPs) have been shown to enter cells via a non-endocytic, non-disruptive pathway that could be valuable for biomedical applications. The same NPs were also found to insert into a series of model cell membranes as a precursor to cellular uptake, but the insertion mechanism remains unclear. Previous simulations have demonstrated that an amphiphilic NP can insert into a single leaflet of a planar lipid bilayer, but in this configuration all charged end groups are localized to one side of the bilayer and it is unknown if further insertion is thermodynamically favorable. Here, we use atomistic molecular dynamics simulations to show that an amphiphilic NP can reach the bilayer midplane non-disruptively if charged ligands iteratively “flip” across the bilayer. Ligand flipping is a favorable process that relaxes bilayer curvature, decreases the nonpolar solvent-accessible surface area of the NP monolayer, and increases attractive ligand-lipid electrostatic interactions. Analysis of end group hydration further indicates that iterative ligand flipping can occur on experimentally relevant timescales. Supported by these results, we present a complete energy landscape for the non-disruptive insertion of amphiphilic NPs into lipid bilayers. These findings will help guide the design of NPs to enhance bilayer insertion and non-endocytic cellular uptake, and also provide physical insight into a possible pathway for the translocation of charged biomacromolecules.
MIT Department
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
10.1371/JOURNAL.PONE.0209492
https://doi.org/10.1371/JOURNAL.PONE.0209492
