Long chain lipids facilitate insertion of large nanoparticles into membranes of small unilamellar vesicles

Insertion of hydrophobic nanoparticles into phospholipid bilayers is limited to small particles that can incorporate into the hydrophobic membrane core in between the two lipid leaflets. Incorporation of nanoparticles above this size limit requires development of challenging surface engineering methodologies. In principle, increasing membrane thickness should facilitate incorporation of larger nanoparticles. Here we explore the effect of very long phospholipids (C24:1) in small unilamellar vesicles, on the membrane insertion efficiency of nanoparticles in the range of 5-13 nm in diameter. To this end, we improved an existing vesicle preparation protocol and utilized cryogenic electron microscopy imaging to examine the mode of interaction and to evaluate the membrane insertion efficiency of membrane-inserted nanoparticles. ### Competing Interest Statement The authors have declared no competing interest.