Integration of Gold Nanoparticles into Bilayer Structures via Adaptive Surface Chemistry

Abstract

We describe the spontaneous incorporation of amphiphilic gold nanoparticles (Au NPs) into the walls of surfactant vesicles. Au NPs were functionalized with mixed monolayers of hydrophilic (deprotonated mercaptoundecanoic acid, MUA) and hydrophobic (octadecanethiol, ODT) ligands, which are known to redistribute dynamically on the NP surface in response to changes in the local environment. When Au NPs are mixed with preformed surfactant vesicles, the hydrophobic ODT ligands on the NP surface interact favorably with the hydrophobic core of the bilayer structure and guide the incorporation of NPs into the vesicle walls. Unlike previous strategies based on small hydrophobic NPs, the present approach allows for the incorporation of water-soluble particles even when the size of the particles greatly exceeds the bilayer thickness. The strategy described here based on inorganic NPs functionalized with two labile ligands should in principle be applicable to other nanoparticle materials and bilayer structures.

Lipid tail protrusions mediate the insertion of nanoparticles into model cell membranes

“…For example, the strong similarity of the AuNP-bilayer fusion process to the pre-stalk transition state for vesicle-vesicle fusion may allow these AuNPs to be used to probe the properties of fusogenic systems. Furthermore, the demonstration of strong thermodynamic forces associated with such insertion provides further evidence that such a process may explain recent experimental observations of non-disruptive association between AuNPs and bilayers 24,25,30,31 . Finally, the fusogenic properties of these AuNPs may present new opportunities for devising novel strategies for endosomal escape, drug delivery, controlled biodistribution and so on, all important research avenues for enhancing treatments based on nanomedicine.…”

“…The thermodynamic driving force for insertion was the hydrophobic effect: the amphiphilic particle surfaces could eliminate waterexposed hydrophobic surface area by inserting into the hydrophobic bilayer core while retaining hydrophilic end groups in aqueous solution by 'snorkelling' 28,29 . Other experimental systems have found such complexation as well 30,31 . Although these previous studies have elucidated the thermodynamics of nanoparticle insertion into lipid bilayers 24,25,32 , the detailed kinetics of the insertion process are still unclear.…”

“…It is likely that AuNP properties such as particle size, ligand composition and ligand length 44 also affect the probability of this hydrophobic contact. However, the key observation that lipid tail protrusions initiate insertion by contacting hydrophobic alkanethiol backbones for both all-MUS and MUS:OT AuNPs indicates that this behaviour may be general to a wide variety of monolayer compositions as this general chemical motif is prominent in a number of AuNP systems 9,10,31,[60][61][62] . Moreover, the strong agreement with experimental results that used polydispserse particle batches with a larger mean core size than used in simulations implies that the pathway is similar for a range of particle core diameters.…”

Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping

“…18 Experimental studies of similar monolayer-protected NPs have observed behavior consistent with bilayer insertion in several other systems. 22−24 Because bilayer insertion requires charged ligand end groups to cross the bilayer, these observations again indicate that charged groups may cross the bilayer more rapidly than anticipated when grafted to a complex material system, although the molecular details of this process are unknown. Understanding how such grafting affects the rate of charge transport could be of great use in drug delivery applications by revealing design guidelines for synthetic materials capable of ferrying water-soluble therapeutic compounds or genetic material across the cell membrane.…”

General and programmable synthesis of hybrid liposome/metal nanoparticles

“…For example, embedded metal nanoparticles larger than ca. 6.5 nm may disrupt the lipid bilayer, resulting in micelle formation ( 21 , 28 , 30 , 31 ). The attachment of the nanoparticles onto the surface of the outer lipid often leads to leakage of the liposome structure ( 32 ).…”