Association Mechanism of Peptide-Coated Metal Nanoparticles with Model Membranes: A Coarse-Grained Study

Functionalized metal nanoparticles (NPs) hold great promise as innovative tools in nanomedicine. However, one of the main challenges is how to optimize their association with the cell membrane, which is critical for their effective delivery. Recent findings show high cellular uptake rates for NPs co...

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Bibliographic Details
Published in:Journal of chemical theory and computation 2021-07, Vol.17 (7), p.4512-4523
Main Authors: Franco-Ulloa, Sebastian, Guarnieri, Daniela, Riccardi, Laura, Pompa, Pier Paolo, De Vivo, Marco
Format: Article
Language:English
Subjects:
Biomolecular Systems
Cell Membrane - chemistry
Cell membranes
Cholesterol
Cholesterol - chemistry
Free energy
HeLa Cells
Humans
Hydrophobic and Hydrophilic Interactions
Lipids
Membrane Lipids - chemistry
Membranes
Metal Nanoparticles - chemistry
Microscopy, Electron, Scanning Transmission
Models, Chemical
Nanoparticles
Peptides
Peptides - chemistry
Scanning transmission electron microscopy
Sterols
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Summary:Functionalized metal nanoparticles (NPs) hold great promise as innovative tools in nanomedicine. However, one of the main challenges is how to optimize their association with the cell membrane, which is critical for their effective delivery. Recent findings show high cellular uptake rates for NPs coated with the polycationic cell-penetrating peptide gH625-644 (gH), although the underlying internalization mechanism is poorly understood. Here, we use extended coarse-grained simulations and free energy calculations to study systems that simultaneously include metal NPs, peptides, lipids, and sterols. In particular, we investigate the first encounter between multicomponent model membranes and 2.5 nm metal NPs coated with gH (gHNPs), based on the evidence from scanning transmission electron microscopy. By comparing multiple membrane and (membranotropic) NP models, we found that gHNP internalization occurs by forming an intermediate state characterized by specific stabilizing interactions formed by peptide-coated nanoparticles with multicomponent model membranes. This association mechanism is mainly characterized by interactions of gH with the extracellular solvent and the polar membrane surface. At the same time, the NP core interacts with the transmembrane (cholesterol-rich) fatty phase.
ISSN:1549-9618
1549-9626
DOI:10.1021/acs.jctc.1c00127