Effects of gold nanoparticles on lipid packing and membrane pore formation

Abstract

Gold nanoparticles (AuNPs) have been increasingly integrated in biological systems, making it imperative to understand their interactions with cell membranes, the first barriers to be crossed to enter cells. Herein, liposomes composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as a model membrane system were treated with citrate stabilized AuNPs from 5 to 30 nm at various concentrations. The fluorescence shifts of Laurdan probes reveal that AuNPs in general made liposomes more fluidic. The increased fluidity is expected to result in an increased surface area, and thus liposome shape changes from circular to less circular, which was further confirmed with fluorescence microscopy. The localized stress in lipids induced by electrostatically adsorbed AuNPs was hypothesized to cause the dominant long-range effect of fluidization of unbound lipid membranes. A secondary effect of the AuNP-induced lateral pressure is the membrane rupture or formation of pores, which was probed by AFM under fluid. We found in this study a nanoparticlemediated approach of modulating the stiffness of lipid membranes: by adsorption of AuNPs, lipids at the binding sites are stiffened whereas lipids afar are fluidized. Understanding the factors that modulate lipid packing is important for the discovery of alternative therapeutic methods for diseases linked to membrane integrity such as high blood pressure and cancer metastasis. The size resemblance of nanoparticles (NPs) to biological macromolecules coupled with the NPs' high surface energy leads to intricate interactions between the two entities. Myriads of study have been conducted to gain insights into the bio-nano interface for biomedical applications.

Probing Interactions between AuNPs/AgNPs and Giant Unilamellar Vesicles (GUVs) Using Hyperspectral Dark-field Microscopy

“…Therefore, we hypothesize that the ability of cations to disrupt the outer layer of lipid membranes occurs at a much greater extent for AuNPs than for AgNPs. Numerous experimental and simulation studies have reported the disruption of lipid bilayers by AuNPs [ 27 , 31 , 32 , 33 , 34 ]. In the mean while when the AuNPs disrupt the outer leaflet of the lipid bilayer, the citrate anions are likely stripped off and left in the aqueous solution as the hydrophobic force between the acyl chains of DMPC and AuNPs outweighs the solvation force.…”

“…The AgNPs (10 nm, 0.02 mg/mL, Sigma-Aldrich #730785) used in this work were prepared by the reduction of silver nitrate and citrate-stabilized in aqueous buffer [ 39 ]. The size of 10 nm was chosen in this study because our earlier work showed that 10-nm AuNPs were most effective in inducing the phase and shape changes in lipid vesicles [ 27 ]. The TEM images of AuNPs and AgNPs ( Figures S1a and S2 ) used in this study and more details on size distribution ( Figure S1b ), concentration and citrate stabilization ( Figure S3 ) can be found in the Supplementary Material .…”

“…In this paper, we report our major findings made with hyperspectral dark-field microscopy on the interactions between citrate stabilized colloidal AuNPs or AgNPs and GUVs of varied composition including pure DMPC to different percent molar concentration of CHOL:DMPC (10, 20, 30 and 40 mol%). The size chosen for both AuNPs and AgNPs was 10 nm, because in our earlier work 10-nm AuNPs were found to be most capable in inducing the phase and shape changes in lipid vesicles [ 27 ]. The findings reported in this work are intended to provide better understanding regarding the mechanisms of AuNP/AgNP and membrane interactions, which are fundamental and critical for their future applications in both therapeutics and diagnostics of cancer.…”

Stimuli‐Responsive Release of Antimicrobials Using Hybrid Inorganic Nanoparticle‐Associated Drug‐Delivery Systems

“…This process has been achieved through the electrostatic interactions that occur between oppositely charged lipid bilayers and NPs as well as through the direct synthesis of NPs on the bilayer surface . The adsorption of charged NPs on the outer surface of liposomes provides an additional benefit of increasing liposomal stability due to electrostatic repulsions between NP‐decorated liposomes of the same charge, which prevents liposomal fusion . Phosphatidylcholines, which possess a zwitterionic headgroup containing a negatively charged phosphate and a positively charged choline, are the most commonly used lipids used to form liposomes.…”

“…[42][43][44][45] The adsorption of charged NPs on the outer surface of liposomes provides an additional benefit of increasing liposomal stability due to electrostatic repulsions between NP-decorated liposomes of the same charge, which prevents liposomal fusion. [46][47][48][49] Phosphatidylcholines, which possess a zwitterionic headgroup containing a negatively charged phosphate and a positively charged choline, are the most commonly used lipids used to form liposomes. Despite the net neutrality of the headgroup, there is a dipole, allowing the electrostatic attraction of charged nanoparticles.…”