The following recent article entitled "Ligand-lipid and ligand-core affinity control the interaction of gold nanoparticles with artificial lipid bilayers and cell membranes "and published (will be published) in Nanomedicine: Nanotechnology, Biology and Medicine
Volume 12, Issue 5, July 2016, Pages 1409–1419 illustrates physical changes as a result of interactions between AuNP and artificial lipid bilayers:
Interactions between nanoparticles (NPs) and biomembranes depend on the physicochemical properties of the NPs, such as size and surface charge. Here we report on the size-dependent interaction of gold nanoparticles (AuNPs), stabilized with ligands differing in charge, i.e. sodium 3-(diphenylphosphino)benzene sulfonate (TPPMS) and sodium 3,3′,3″-triphenylphosphine sulfonate (TPPTS), respectively, with artificial membranes (black lipid membranes; BLMs) and HeLa cells. The TPPTS-stabilized AuNPs affect BLMs at lower size than TPPMS-stabilized ones. On HeLa cells we found decreasing cytotoxicity with increasing particle size, however, with an overall lower cytotoxicity for TPPTS-stabilized AuNPs. We attribute size-dependent BLM properties as well as reduced cytotoxicity of TPPTS-stabilized AuNPs to weaker shielding of the AuNP core when stabilized with TPPTS. We hypothesize that the partially unshielded hydrophobic gold core can embed into the hydrophobic membrane interior. Thereby we demonstrate that ligand-dependent cytotoxicity of NP can occur even when the NPs are not translocated through the membrane.
Size dependence of gold nanoparticle interactions with a supported lipid bilayer: A QCM-D study
Christina M. Baileya, Elaheh Kamalooa, Kellie L. Watermana, Kathleen F. Wanga, b,
Ramanathan Nagarajanb, , , Terri A. Camesanoa, ,
doi:10.1016/j.bpc.2015.05.006
Highlights
Lipid bilayer membrane - gold nanoparticle interactions were examined using QCM-D.
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The influence of an environmental polymer over these interactions was explored.
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In the absence of the polymer, the nanoparticles did not perturb the membrane.
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With the polymer present, larger nanoparticles were found to disrupt the membrane.
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The particle size dependence of polymer-mediated membrane disruption is modeled.
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Cytotoxicity due to factors external to the nanoparticle marks a paradigm shift.
Abstract
Knowledge of nanoparticle (NP)–membrane interactions is important to advances in nanomedicine as well as for determining the safety of NPs to humans and the ecosystem. This study focuses on a unique mechanism of cytotoxicity, cell membrane destabilization, which is principally dependent on the nanoparticle nature of the material rather than on its molecular properties. We investigated the interactions of 2, 5, 10, and 40 nm gold NPs with supported lipid bilayer (SLB) of L-α-phosphatidylcholine using quartz crystal microbalance with dissipation monitoring (QCM-D). Gold NPs were tested both in the absence of and in the presence of polymethacrylic acid (PMAA), used to simulate the natural organic matter (NOM) in the environment. In the absence of PMAA, for all NP sizes, we observed only small mass losses (1 to 6 ng) from the membrane. This small lipid removal may be a free energy lowering mechanism to relieve stresses induced by the adsorption of NPs, with the changes too small to affect the membrane integrity. In the presence of PMAA, we observed a net mass increase in the case of smaller NPs. We suggest that the increased adhesion between the NP and the bilayer, promoted by PMAA, causes sufficient NP adsorption on the bilayer to overcompensate for any loss of lipid. The most remarkable observation is the significant mass loss (60 ng) for the case of 40 nm NPs. We attribute this to the lipid bilayer engulfing the NP and leaving the crystal surface. We propose a simple phenomenological model to describe the competition between the particle-bilayer adhesion energy, the bilayer bending energy, and the interfacial energy at bilayer defect edges. The model shows that the larger NPs, which become more adhesive because of the polymer adsorption, are engulfed by the bilayer and leave the crystal surface, causing large mass loss and membrane disruption. The QCM-D measurements thus offer direct evidence that even if NPs are intrinsically not cytotoxic, they can become cytotoxic in the presence of environmental organic matter which modulates the adhesive interactions between the nanoparticle and the membrane.
Herein other 5 recent publications on the topic of concern.
3-Effect of Gold Nanoparticle on Structure and Fluidity of Lipid Membrane
Anil R. Mhashal, Sudip Roy
PLOS ONE
Published: December 3, 2014
http://dx.doi.org/10.1371/journal.pone.0114152
Abstract
This paper deals with the effect of different size gold nanoparticles on the fluidity of lipid membrane at different regions of the bilayer. To investigate this, we have considered significantly large bilayer leaflets and incorporated only one nanoparticle each time, which was subjected to all atomistic molecular dynamics simulations. We have observed that, lipid molecules located near to the gold nanoparticle interact directly with it, which results in deformation of lipid structure and slower dynamics of lipid molecules. However, lipid molecules far away from the interaction site of the nanoparticle get perturbed, which gives rise to increase in local ordering of the lipid domains and decrease in fluidity. The bilayer thickness and area per head group in this region also get altered. Similar trend, but with different magnitude is also observed when different size nanoparticle interact with the bilayer.
4-Interaction of amphiphilic gold nanoparticles with lipid membranes and their application to cancer radiotherapy
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Author: Yang, Yu-Sang
Citable URI: http://hdl.handle.net/1721.1/81061
Other Contributors: Massachusetts Institute of Technology. Department of Materials Science and Engineering.
Advisor: Darrell J. Irvine.
Department: Massachusetts Institute of Technology. Department of Materials Science and Engineering.
Publisher: Massachusetts Institute of Technology
Date Issued: 2013
Abstract:
Striped gold nanoparticles (NPs), inorganic particles protected by an amphiphilic mixed organic ligand shell, are the most recent and potent evolution of gold nanoparticle intracellular delivery vectors. Here we propose the combination of striped gold nanoparticles with lipid vesicles of diameter < 200 nm in order to concentrate their delivery and couple their delivery to the delivery of pharmaceuticals. Mechanisms of penetration of striped gold nanoparticles into live cell membranes via non-endocytic pathways was poorly understood, therefore this work focuses on the interaction of striped NPs with synthetic lipid membranes as models for cellular membranes, and interactions with bacterial membranes have been investigated to provide a more stringent test of their interaction capacity. Cellular uptake of striped gold nanoparticles has been observed to be homogeneous when delivered via interbilayer crosslinked multilamellar lipid vesicles, which resulted in enhancement of striped gold nanoparticle induced radiosensitization causing membrane rupture and genomic damage.
https://dspace.mit.edu/handle/1721.1/81061
5- Size-Dependent Interaction between Gold Nanoparticles and Lipid Bilayer Membranes
Julia Setzler, Janine Broda, Annika Leifert, Ulrich Simon, Roland Benz, Wolfgang Wenzel
Open Archive
DOI: http://dx.doi.org/10.1016/j.bpj.2012.11.2370
Summary
Full Text
Metal nanoparticles, in particular gold nanoparticles (AuNPs) are of great interest in biomedical research, such as in diagnosis and therapeutics[1]. Recent studies indicate the size-dependent cytotoxicity of the AuNPs[2], however the means of membrane association and interaction are currently unknown. To better understand and optimize these novel compounds, their interactions with biological membranes need to be investigated. We used AuNPs stabilized by triphenylphosphine derivatives ranging in size from 1.4 to 15 nm size in bilayer experiments [3].
6- Penetration of Lipid Membranes by Gold Nanoparticles: Insights into Cellular Uptake, Cytotoxicity, and Their Relationship
Jiaqi Lin†, Hongwu Zhang†*, Zhen Chen†‡, and Yonggang Zheng†
† State Key Laboratory of Structure Analysis for Industrial Equipment, Department of Engineering Mechanics, Faculty of Vehicle Engineering and Mechanics, Dalian University of Technology, Dalian 116024, P. R. China
‡ Department of Civil and Environmental Engineering, University of Missouri, Columbia, Missouri 65211-2200
Nanoparticle penetration into cell membranes is an interesting phenomenon that may have crucial implications on the nanoparticles’ biomedical applications. In this paper, a coarse-grained model for gold nanoparticles (AuNPs) is developed (verified against experimental data available) to simulate their interactions with model lipid membranes. Simulations reveal that AuNPs with different signs and densities of surface charges spontaneously adhere to the bilayer surface or penetrate into the bilayer interior. The potential of mean force calculations show that the energy gains upon adhesion or penetration is significant. In the case of penetration, it is found that defective areas are induced across the entire surface of the upper leaflet of the bilayer and a hydrophilic pore that transports water molecules was formed with its surrounding lipids highly disordered. Penetration and its concomitant membrane disruptions can be a possible mechanism of the two observed phenomena in experiments: AuNPs bypass endocytosis during their internalization into cells and cytotoxicity of AuNPs. It is also found that both the level of penetration and membrane disruption increase as the charge density of the AuNP increases, but in different manners. The findings suggest a way of controlling the AuNP−cell interactions by manipulating surface charge densities of AuNPs to achieve designated goals in their biomedical applications, such as striking a balance between their cellular uptake and cytotoxicity in order to achieve optimal delivery efficiency as delivery agents.
http://pubs.acs.org/doi/abs/10.1021/nn1010792
7- Ligand-lipid and ligand-core affinity control the interaction of gold nanoparticles with artificial lipid bilayers and cell membranes
Janine Broda, Dr. rer. nat.1 ,Julia Setzler, Dr. rer. nat.1 ,Annika Leifert, Dr. rer. nat.
,Julia Steitz, Dr. rer. nat. ,Roland Benz, Dr. rer. nat. ,Ulrich Simon, Dr. rer. nat.
Interactions between nanoparticles (NPs) and biomembranes depend on the physicochemical properties of the NPs, such as size and surface charge. Here we report on the size-dependent interaction of gold nanoparticles (AuNPs), stabilized with ligands differing in charge, i.e. sodium 3-(diphenylphosphino)benzene sulfonate (TPPMS) and sodium 3,3′,3″-triphenylphosphine sulfonate (TPPTS), respectively, with artificial membranes (black lipid membranes; BLMs) and HeLa cells. The TPPTS-stabilized AuNPs affect BLMs at lower size than TPPMS-stabilized ones. On HeLa cells we found decreasing cytotoxicity with increasing particle size, however, with an overall lower cytotoxicity for TPPTS-stabilized AuNPs. We attribute size-dependent BLM properties as well as reduced cytotoxicity of TPPTS-stabilized AuNPs to weaker shielding of the AuNP core when stabilized with TPPTS. We hypothesize that the partially unshielded hydrophobic gold core can embed into the hydrophobic membrane interior. Thereby we demonstrate that ligand-dependent cytotoxicity of NP can occur even when the NPs are not translocated through the membrane.