title: Aromaticity/Bulkiness of Surface Ligands to Promote the Interaction of Anionic Amphiphilic Gold Nanoparticles with Lipid Bilayers.
abstract: The presence of large hydrophobic aromatic residues in cell-penetrating peptides or proteins has been demonstrated to be advantageous for their cell penetration. This phenomenon has also been observed when AuNPs were modified with peptides containing aromatic amino acids. However, it is still not clear how the presence of hydrophobic and aromatic groups on the surface of anionic AuNPs affects their interaction with lipid bilayers. Here, we studied the interaction of a range of anionic amphiphilic AuNPs coated by different combinations of hydrophobic and anionic ligands with four different types of synthetic lipid vesicles. Our results demonstrated the important role of the surface aromatic or bulky groups, relative to the hydrocarbon chains, in the interaction of anionic AuNPs with lipid bilayers. Hydrophobic interaction itself arising from the insertion of aromatic/bulky ligands on the surface of AuNPs into lipid bilayers is sufficiently strong to cause overt disruption of lipid vesicles and cell membranes. Moreover, by comparing the results obtained from AuNPs coated with aromatic ligands and cyclohexyl ligands lacking aromaticity respectively, we demonstrated that the bulkiness of the terminal groups in hydrophobic ligands instead of the aromatic character might be more important to the interaction of AuNPs with lipid bilayers. Finally, we further correlated the observation on model liposomes with that on cell membranes, demonstrating that AuNPs that are more disruptive to the more negatively charged liposomes are also substantially more disruptive to cell membranes. In addition, our results revealed that certain cellular membrane domains that are more susceptible to disruption caused by hydrophobic interactions with nanoparticle surfaces might determine the threshold of AuNP-mediated cytotoxicity.
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, 361005, P.R. China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Gao
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, 361005, P.R. China.
authors.forename: Ouyang
authors.initials: O
authors.lastname: Zhang
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, 361005, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ren
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, 361005, P.R. China.
authors.forename: Chuanliu
authors.initials: C
authors.lastname: Wu
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, 361005, P.R. China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000067493:Dynamic Light Scattering; D005227:Fatty Acids / Q000737:chemistry; D005452:Fluoresceins; D006046:Gold / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D008744:Methylamines / Q000737:chemistry; D009829:Oleic Acids / Q000737:chemistry; D010713:Phosphatidylcholines; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry*; D014363:Tryptamines / Q000737:chemistry
chemical_list: C505222:11-mercaptoundecanoic acid; C000614832:2-((2,3-bis(oleoyloxy)propyl)dimethylammonio)ethyl hydrogen phosphate; D005227:Fatty Acids; D005452:Fluoresceins; D008024:Ligands; D008051:Lipid Bilayers; D008081:Liposomes; D008744:Methylamines; D009829:Oleic Acids; D010713:Phosphatidylcholines; D013438:Sulfhydryl Compounds; D013501:Surface-Active Agents; D014363:Tryptamines; C086974:hexadecanethiol; C024098:6-carboxyfluorescein; C030820:tryptamine; D006046:Gold; C017251:1,2-oleoylphosphatidylcholine