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 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.

Interfacing the Cell with "Biomimetic Membrane Proteins".

Integral membrane proteins mediate a myriad of cellular processes and are the target of many therapeutic drugs. Enhancement and extension of the functional scope of membrane proteins can be realized by membrane incorporation of engineered nanoparticles designed for specific diagnostic and therapeutic applications. In contrast to hydrophobic insertion of small amphiphilic molecules, delivery and membrane incorporation of particles on the nanometric scale poses a crucial barrier for technological development. In this perspective, the transformative potential of biomimetic membrane proteins (BMPs), current state of the art, and the barriers that need to be overcome in order to advance the field are discussed.