Control of Lipid Bilayer Phases of Cell-Sized Liposomes by Surface-Engineered Plasmonic Nanoparticles

Abstract

Liquid-ordered (Lo)-phase domains, a cholesterol-rich area on lipid bilayers, have attracted significant attention recently because of their relevance to lipid rafts, the formation/collapse of which is associated with various kinds of information exchange through the plasma membrane. Here, we demonstrate that the formation/collapse of Lophase domains in cell-sized liposomes, that is, giant unilamellar vesicles (GUVs), can be controlled with bioactive plasmonic nanoparticles and light. The nanoparticles were prepared by surface modification of gold nanorods (AuNRs) using a cationized mutant of high-density lipoprotein (HDL), which is a natural cholesterol transporter. Upon the addition of surface-engineered AuNRs to GUVs with the mixed domains of Lo and liquid-disorder (Ld) phases, the Lo domains collapsed and solid-ordered (So)-phase domains were formed. The reverse phase transition was achieved photothermally, with the AuNRs loaded with cholesterol. During these transitions, the AuNRs appeared to be selectively localized on the less fluidic domain (Lo or So) in the phase-mixed GUVs. These results indicate that the phase transitions occur through the membrane binding of the AuNRs followed by spontaneous/photothermal transfer of cholesterol between the AuNRs and GUVs. Our strategy to develop bioactive AuNRs potentially enables spatiotemporal control of the formation/collapse of lipid rafts in living cells.

Observation and Analysis of Model Lipid Raft Deformation Dynamics Induced by Lipoprotein–Gold Nanorod-based Devices to Manipulate Phase Transition of Lipid Bilayer

“…The preparation of catHDL was described in a previous report 30,33 . In brief, POPC and DOTAP solutions in ethanol were mixed in a round-bottom flask in a molar ratio of 7:3.…”

“…AuNRs were synthesized by the seedless method. 30,53 In this method, 1200 µL of a 4-mM aqueous solution of AgNO3, 400 µL of a 50-mM aqueous solution of HAuCl4, and 258 µL of a 100-mM solution of aqueous L-ascorbic acid are added to 40 mL of a 0.1-M aqueous solution of CTAB.…”

“…[26][27][28][29] Furthermore, not many studies have investigated the interaction between the interface and GUVs for domain formation/deformation. [30][31][32] Recently, we developed the first biocompatible nanodevice to regulate the formation/deformation of model lipid rafts. 30 The nanodevice is composed of a gold nanorod (AuNR) and a cationic highdensity lipoprotein (HDL) (Figure 1A).…”

“…[30][31][32] Recently, we developed the first biocompatible nanodevice to regulate the formation/deformation of model lipid rafts. 30 The nanodevice is composed of a gold nanorod (AuNR) and a cationic highdensity lipoprotein (HDL) (Figure 1A). 33,34 The surface of the AuNR was coated with an HDLoriginated lipid-protein complex layer.…”

“…We showed that the nanodevice can control Lo-to-So phase transition by cholesterol absorption and material adhesion and that it photo-regulates Soto-Lo phase transition induced by cholesterol supplements from previously prepared cholesterolsaturated pm-AuNRs. 30 In this study, we evaluated the phase transition process triggered by pm-AuNRs and analyzed the morphological changes of Lo domains through phase transition. We monitored the phase separation process and found that the domain boundary was unsettled and mixed in some local areas.…”