Cationic Au Nanoparticle Binding with Plasma Membrane-like Lipid Bilayers: Potential Mechanism for Spontaneous Permeation to Cells Revealed by Atomistic Simulations

E. Heikkila, H. Martinez-Seara, A. A. Gurtovenko, M. Javanainen, H. Hakkinen, I. Vattulainen, J. Akola

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Resumé

Despite 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 cooperative 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 k(B)T 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.
OriginalsprogEngelsk
TidsskriftJournal of Physical Chemistry C
Vol/bind118
Udgave nummer20
Sider (fra-til)11131-11141
ISSN1932-7447
DOI
StatusUdgivet - 2014

Citer dette

Heikkila, E. ; Martinez-Seara, H. ; Gurtovenko, A. A. ; Javanainen, M. ; Hakkinen, H. ; Vattulainen, I. ; Akola, J. / Cationic Au Nanoparticle Binding with Plasma Membrane-like Lipid Bilayers: Potential Mechanism for Spontaneous Permeation to Cells Revealed by Atomistic Simulations. I: Journal of Physical Chemistry C. 2014 ; Bind 118, Nr. 20. s. 11131-11141.
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title = "Cationic Au Nanoparticle Binding with Plasma Membrane-like Lipid Bilayers: Potential Mechanism for Spontaneous Permeation to Cells Revealed by Atomistic Simulations",
abstract = "Despite 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 cooperative 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 k(B)T 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.",
author = "E. Heikkila and H. Martinez-Seara and Gurtovenko, {A. A.} and M. Javanainen and H. Hakkinen and I. Vattulainen and J. Akola",
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Cationic Au Nanoparticle Binding with Plasma Membrane-like Lipid Bilayers: Potential Mechanism for Spontaneous Permeation to Cells Revealed by Atomistic Simulations. / Heikkila, E.; Martinez-Seara, H.; Gurtovenko, A. A.; Javanainen, M.; Hakkinen, H.; Vattulainen, I.; Akola, J.

I: Journal of Physical Chemistry C, Bind 118, Nr. 20, 2014, s. 11131-11141.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Cationic Au Nanoparticle Binding with Plasma Membrane-like Lipid Bilayers: Potential Mechanism for Spontaneous Permeation to Cells Revealed by Atomistic Simulations

AU - Heikkila, E.

AU - Martinez-Seara, H.

AU - Gurtovenko, A. A.

AU - Javanainen, M.

AU - Hakkinen, H.

AU - Vattulainen, I.

AU - Akola, J.

PY - 2014

Y1 - 2014

N2 - Despite 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 cooperative 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 k(B)T 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.

AB - Despite 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 cooperative 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 k(B)T 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.

U2 - 10.1021/jp5024026

DO - 10.1021/jp5024026

M3 - Journal article

VL - 118

SP - 11131

EP - 11141

JO - The Journal of Physical Chemistry Part C

JF - The Journal of Physical Chemistry Part C

SN - 1932-7447

IS - 20

ER -