title: Lipid tail protrusions mediate the insertion of nanoparticles into model cell membranes.
abstract: Recent work has demonstrated that charged gold nanoparticles (AuNPs) protected by an amphiphilic organic monolayer can spontaneously insert into the core of lipid bilayers to minimize the exposure of hydrophobic surface area to water. However, the kinetic pathway to reach the thermodynamically stable transmembrane configuration is unknown. Here, we use unbiased atomistic simulations to show the pathway by which AuNPs spontaneously insert into bilayers and confirm the results experimentally on supported lipid bilayers. The critical step during this process is hydrophobic-hydrophobic contact between the core of the bilayer and the monolayer of the AuNP that requires the stochastic protrusion of an aliphatic lipid tail into solution. This last phenomenon is enhanced in the presence of high bilayer curvature and closely resembles the putative pre-stalk transition state for vesicle fusion. To the best of our knowledge, this work provides the first demonstration of vesicle fusion-like behaviour in an amphiphilic nanoparticle system.
authors.affiliation: 1] Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2].
authors.forename: Reid C
authors.initials: RC
authors.lastname: Van Lehn
authors.affiliation: 1] Institute of Materials, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland [2].
authors.forename: Maria
authors.initials: M
authors.lastname: Ricci
authors.affiliation: Institute of Materials, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Paulo H J
authors.initials: PH
authors.lastname: Silva
authors.affiliation: IRCCS Foundation Institute for Neurology 'Carlo Besta', IFOM-IEO-Campus, 20139 Milan, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Andreozzi
authors.affiliation: Institute of Materials, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Javier
authors.initials: J
authors.lastname: Reguera
authors.affiliation: Department of Physics, Durham University, South Road, Durham DH1 3LE, UK.
authors.forename: Kislon
authors.initials: K
authors.lastname: Voïtchovsky
authors.affiliation: Institute of Materials, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Stellacci
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Alexander-Katz
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D006046:Gold; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008055:Lipids; D010713:Phosphatidylcholines; D006046:Gold; C017251:1,2-oleoylphosphatidylcholine