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ARTICLE
Received 14 Nov 2013 | Accepted 23 Jun 2014 | Published 21 Jul 2014 DOI: 10.1038/ncomms5482
Lipid tail protrusions mediate the insertion
of nanoparticles into model cell membranes
1, 2, 2 3 2 4
Reid C. Van Lehn *, Maria Ricci *, Paulo H.J. Silva , Patrizia Andreozzi , Javier Reguera , Kislon Voı¨tchovsky ,
Francesco Stellacci2 Alfredo Alexander-Katz1
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.
1 Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. 2 Institute of Materials,
´ ´ 3
Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland. IRCCS Foundation Institute for Neurology ‘Carlo Besta’, IFOM-IEO-Campus, 20139
Milan
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