Long-Chain Lipids Facilitate Insertion of Large Nanoparticles into Membranes of Small Unilamellar Vesicles

Langmuir. 2024 May 21;40(20):10477-10485. doi: 10.1021/acs.langmuir.3c03471. Epub 2024 May 6.

Abstract

Insertion of hydrophobic nanoparticles into phospholipid bilayers is limited to small particles that can incorporate into a hydrophobic membrane core between two lipid leaflets. Incorporation of nanoparticles above this size limit requires the development of challenging surface engineering methodologies. In principle, increasing the long-chain lipid component in the lipid mixture should facilitate incorporation of larger nanoparticles. Here, we explore the effect of incorporating very long phospholipids (C24:1) into small unilamellar vesicles on the membrane insertion efficiency of hydrophobic nanoparticles that are 5-11 nm in diameter. To this end, we improve an existing vesicle preparation protocol and utilized cryogenic electron microscopy imaging to examine the mode of interaction and evaluate the insertion efficiency of membrane-inserted nanoparticles. We also perform classical coarse-grained molecular dynamics simulations to identify changes in lipid membrane structural properties that may increase insertion efficiency. Our results indicate that long-chain lipids increase the insertion efficiency by preferentially accumulating near membrane-inserted nanoparticles to reduce the thermodynamically unfavorable disruption of the membrane.

MeSH terms

  • Hydrophobic and Hydrophilic Interactions
  • Lipid Bilayers / chemistry
  • Nanoparticles* / chemistry
  • Particle Size
  • Phospholipids / chemistry
  • Unilamellar Liposomes* / chemistry