000154397 001__ 154397 000154397 005__ 20210129213907.0 000154397 0247_ $$2doi$$a10.1021/jp5024026 000154397 0247_ $$2ISSN$$a1932-7447 000154397 0247_ $$2ISSN$$a1932-7455 000154397 0247_ $$2WOS$$aWOS:000336509400068 000154397 037__ $$aFZJ-2014-03744 000154397 082__ $$a540 000154397 1001_ $$0P:(DE-HGF)0$$aHeikkilä, Elena$$b0$$eCorresponding Author 000154397 245__ $$aCationic Au Nanoparticle Binding with Plasma Membrane-like Lipid Bilayers: Potential Mechanism for Spontaneous Permeation to Cells Revealed by Atomistic Simulations 000154397 260__ $$aWashington, DC$$bSoc.$$c2014 000154397 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1404914396_32146 000154397 3367_ $$2DataCite$$aOutput Types/Journal article 000154397 3367_ $$00$$2EndNote$$aJournal Article 000154397 3367_ $$2BibTeX$$aARTICLE 000154397 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000154397 3367_ $$2DRIVER$$aarticle 000154397 520__ $$aDespite being chemically inert as a bulk material, nanoscale gold can pose harmful side effects to living organisms. In particular, cationic Au nanoparticles (AuNP+) of 2 nm diameter or less permeate readily through plasma membranes and induce cell death. We report atomistic simulations of cationic Au nanoparticles interacting with realistic membranes and explicit solvent using a model system that comprises two cellular compartments, extracellular and cytosolic, divided by two asymmetric lipid bilayers. The membrane–AuNP+ binding and membrane reorganization processes are discovered to be governed by co-operative effects where AuNP+, counterions, water, and the two membrane leaflets all contribute. On the extracellular side, we find that the nanoparticle has to cross a free energy barrier of about 5 kBT prior forming a stable contact with the membrane. This results in a rearrangement of the zwitterionic lipids and nanoparticle side groups in the contact area, giving rise to the initial stage of pore formation on the membrane surface. Such behavior is not seen on the cytosolic side, where AuNP+ is spontaneously captured by the negatively charged phosphatidylserine lipids that diffuse to enrich the membrane leaflet underneath AuNP+, further pointing to AuNP+ accumulation on the inner leaflet of a plasma membrane. The results suggest AuNP+ permeation to take place through the formation of a pore together with partial nanoparticle neutralization/deprotonation, leading to membrane disruption at higher nanoparticle concentrations. The data also suggest a potential mechanism for cytotoxicity as AuNP+ binding to the extracellular leaflet may trigger apoptosis through translocation of phosphatidylserine. 000154397 536__ $$0G:(DE-HGF)POF2-422$$a422 - Spin-based and quantum information (POF2-422)$$cPOF2-422$$fPOF II$$x0 000154397 588__ $$aDataset connected to CrossRef, juser.fz-juelich.de 000154397 7001_ $$0P:(DE-HGF)0$$aMartinez-Seara, Hector$$b1 000154397 7001_ $$0P:(DE-HGF)0$$aGurtovenko, Andrey A.$$b2 000154397 7001_ $$0P:(DE-HGF)0$$aJavanainen, Matti$$b3 000154397 7001_ $$0P:(DE-HGF)0$$aHäkkinen, Hannu$$b4 000154397 7001_ $$0P:(DE-HGF)0$$aVattulainen, Ilpo$$b5 000154397 7001_ $$0P:(DE-Juel1)130496$$aAkola, Jaakko$$b6$$ufzj 000154397 773__ $$0PERI:(DE-600)2256522-X$$a10.1021/jp5024026$$gVol. 118, no. 20, p. 11131 - 11141$$n20$$p11131 - 11141$$tThe @journal of physical chemistry <Washington, DC> / C$$v118$$x1932-7455$$y2014 000154397 8564_ $$uhttps://juser.fz-juelich.de/record/154397/files/FZJ-2014-03744.pdf$$yRestricted$$zPublished final document. 000154397 909CO $$ooai:juser.fz-juelich.de:154397$$pVDB 000154397 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)130496$$aForschungszentrum Jülich GmbH$$b6$$kFZJ 000154397 9132_ $$0G:(DE-HGF)POF3-142$$1G:(DE-HGF)POF3-140$$2G:(DE-HGF)POF3-100$$aDE-HGF$$bForschungsbereich Energie$$lFuture Information Technology - Fundamentals, Novel Concepts and Energy Efficiency (FIT)$$vControlling Spin-Based Phenomena$$x0 000154397 9132_ $$0G:(DE-HGF)POF3-143$$1G:(DE-HGF)POF3-140$$2G:(DE-HGF)POF3-100$$aDE-HGF$$bForschungsbereich Energie$$lFuture Information Technology - Fundamentals, Novel Concepts and Energy Efficiency (FIT)$$vControlling Configuration-Based Phenomena$$x1 000154397 9131_ $$0G:(DE-HGF)POF2-422$$1G:(DE-HGF)POF2-420$$2G:(DE-HGF)POF2-400$$3G:(DE-HGF)POF2$$4G:(DE-HGF)POF$$aDE-HGF$$bSchlüsseltechnologien$$lGrundlagen zukünftiger Informationstechnologien$$vSpin-based and quantum information$$x0 000154397 9141_ $$y2014 000154397 915__ $$0StatID:(DE-HGF)0010$$2StatID$$aJCR/ISI refereed 000154397 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR 000154397 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000154397 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000154397 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000154397 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000154397 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000154397 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000154397 915__ $$0StatID:(DE-HGF)1020$$2StatID$$aDBCoverage$$bCurrent Contents - Social and Behavioral Sciences 000154397 9201_ $$0I:(DE-Juel1)PGI-1-20110106$$kPGI-1$$lQuanten-Theorie der Materialien$$x0 000154397 980__ $$ajournal 000154397 980__ $$aVDB 000154397 980__ $$aI:(DE-Juel1)PGI-1-20110106 000154397 980__ $$aUNRESTRICTED