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

Adan Marzouq, Lion Morgenstein, Carlos A. Huang-Zhu, Shimon Yudovich, Ayelet Atkins, Asaf Grupi, Reid C. Van Lehn, Shimon Weiss

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)10477-10485
Number of pages9
Issue number20
StatePublished - 21 May 2024

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