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Title: Preferential interactions of primary amine-terminated quantum dots with membrane domain boundaries and lipid rafts revealed with nanometer resolution

Abstract

The initial interactions of engineered nanoparticles (NPs) with living cells are governed by physicochemical properties of the NP and the molecular composition and structure of the cell membrane. Eukaryotic cell membranes contain lipid rafts – liquid-ordered nanodomains involved in membrane trafficking and molecular signaling. However, the impact of these membrane structures on cellular interactions of NPs remains unclear. Here we investigate the role of membrane domains in the interactions of primary amine-terminated quantum dots (Qdots) with liquid-ordered domains or lipid rafts in model membranes and intact cells, respectively. Using correlative atomic force and fluorescence microscopy, we found that the Qdots preferentially localized to boundaries between liquid-ordered and liquid-disordered phases in supported bilayers. The Qdots also induced holes at these phase boundaries. Using super resolution fluorescence microscopy (STORM), we found that the Qdots preferentially co-localized with lipid rafts in the membrane of intact trout gill epithelial cells – a model cell type for environmental exposures. Our observations uncovered preferential interactions of amine-terminated Qdots with liquid-ordered domains and their boundaries, possibly due to membrane curvature at phase boundaries creating energetically favorable sites for NP interactions. The preferential interaction of the Qdots with lipid rafts supports their potential internalization via lipid raft-mediated endocytosismore » and interactions with raft-resident signaling molecules.« less

Authors:
ORCiD logo [1]; ORCiD logo [1];  [2];  [2];  [2];  [1]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [2]; ORCiD logo [1]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
  2. Univ. of Wisconsin, Milwaukee, WI (United States). Dept. of Chemistry
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1597658
Report Number(s):
PNNL-SA-146870
Journal ID: ISSN 2051-8153; ESNNA4
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
Environmental Science: Nano
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2051-8153
Publisher:
Royal Society of Chemistry
Country of Publication:
United States
Language:
English
Subject:
77 NANOSCIENCE AND NANOTECHNOLOGY

Citation Formats

Mensch, Arielle C., Melby, Eric S., Laudadio, Elizabeth D., Foreman-Ortiz, Isabel U., Zhang, Yongqian, Dohnalkova, Alice, Hu, Dehong, Pedersen, Joel A., Hamers, Robert J., and Orr, Galya. Preferential interactions of primary amine-terminated quantum dots with membrane domain boundaries and lipid rafts revealed with nanometer resolution. United States: N. p., 2019. Web. doi:10.1039/C9EN00996E.
Mensch, Arielle C., Melby, Eric S., Laudadio, Elizabeth D., Foreman-Ortiz, Isabel U., Zhang, Yongqian, Dohnalkova, Alice, Hu, Dehong, Pedersen, Joel A., Hamers, Robert J., & Orr, Galya. Preferential interactions of primary amine-terminated quantum dots with membrane domain boundaries and lipid rafts revealed with nanometer resolution. United States. doi:10.1039/C9EN00996E.
Mensch, Arielle C., Melby, Eric S., Laudadio, Elizabeth D., Foreman-Ortiz, Isabel U., Zhang, Yongqian, Dohnalkova, Alice, Hu, Dehong, Pedersen, Joel A., Hamers, Robert J., and Orr, Galya. Mon . "Preferential interactions of primary amine-terminated quantum dots with membrane domain boundaries and lipid rafts revealed with nanometer resolution". United States. doi:10.1039/C9EN00996E. https://www.osti.gov/servlets/purl/1597658.
@article{osti_1597658,
title = {Preferential interactions of primary amine-terminated quantum dots with membrane domain boundaries and lipid rafts revealed with nanometer resolution},
author = {Mensch, Arielle C. and Melby, Eric S. and Laudadio, Elizabeth D. and Foreman-Ortiz, Isabel U. and Zhang, Yongqian and Dohnalkova, Alice and Hu, Dehong and Pedersen, Joel A. and Hamers, Robert J. and Orr, Galya},
abstractNote = {The initial interactions of engineered nanoparticles (NPs) with living cells are governed by physicochemical properties of the NP and the molecular composition and structure of the cell membrane. Eukaryotic cell membranes contain lipid rafts – liquid-ordered nanodomains involved in membrane trafficking and molecular signaling. However, the impact of these membrane structures on cellular interactions of NPs remains unclear. Here we investigate the role of membrane domains in the interactions of primary amine-terminated quantum dots (Qdots) with liquid-ordered domains or lipid rafts in model membranes and intact cells, respectively. Using correlative atomic force and fluorescence microscopy, we found that the Qdots preferentially localized to boundaries between liquid-ordered and liquid-disordered phases in supported bilayers. The Qdots also induced holes at these phase boundaries. Using super resolution fluorescence microscopy (STORM), we found that the Qdots preferentially co-localized with lipid rafts in the membrane of intact trout gill epithelial cells – a model cell type for environmental exposures. Our observations uncovered preferential interactions of amine-terminated Qdots with liquid-ordered domains and their boundaries, possibly due to membrane curvature at phase boundaries creating energetically favorable sites for NP interactions. The preferential interaction of the Qdots with lipid rafts supports their potential internalization via lipid raft-mediated endocytosis and interactions with raft-resident signaling molecules.},
doi = {10.1039/C9EN00996E},
journal = {Environmental Science: Nano},
number = 1,
volume = 7,
place = {United States},
year = {2019},
month = {12}
}

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Works referenced in this record:

Dynamic atomic force microscopy methods
journal, September 2002


Nanomaterials and Global Sustainability
journal, March 2017


Passive Transport of C 60 Fullerenes through a Lipid Membrane:  A Molecular Dynamics Simulation Study
journal, February 2008

  • Bedrov, Dmitry; Smith, Grant D.; Davande, Hemali
  • The Journal of Physical Chemistry B, Vol. 112, Issue 7
  • DOI: 10.1021/jp075149c

Nanoscale Heterogeneities Drive Enhanced Binding and Anomalous Diffusion of Nanoparticles in Model Biomembranes
journal, January 2018


Mechanisms of Quantum Dot Nanoparticle Cellular Uptake
journal, May 2009

  • Zhang, Leshuai W.; Monteiro-Riviere, Nancy A.
  • Toxicological Sciences, Vol. 110, Issue 1
  • DOI: 10.1093/toxsci/kfp087

Nanoparticles Meet Cell Membranes: Probing Nonspecific Interactions using Model Membranes
journal, December 2013

  • Chen, Kai Loon; Bothun, Geoffrey D.
  • Environmental Science & Technology, Vol. 48, Issue 2
  • DOI: 10.1021/es403864v

Correlated Fluorescence-Atomic Force Microscopy of Membrane Domains: Structure of Fluorescence Probes Determines Lipid Localization
journal, March 2006


Partitioning of nanoscale particles on a heterogeneous multicomponent lipid bilayer
journal, January 2018

  • Yang, Kai; Yang, Ran; Tian, Xiaodong
  • Physical Chemistry Chemical Physics, Vol. 20, Issue 44
  • DOI: 10.1039/C8CP05710A

Real-Time Analysis of the Effects of Cholesterol on Lipid Raft Behavior Using Atomic Force Microscopy
journal, March 2003


Crystalline Hydration Structure at the Membrane–Fluid Interface of Model Lipid Rafts Indicates a Highly Reactive Boundary Region
journal, November 2011

  • Sheikh, Khizar H.; Jarvis, Suzanne P.
  • Journal of the American Chemical Society, Vol. 133, Issue 45
  • DOI: 10.1021/ja2068142

Toxic Potential of Materials at the Nanolevel
journal, February 2006


The Intrinsic Resolution Limit in the Atomic Force Microscope: Implications for Heights of Nano-Scale Features
journal, August 2011


Cholesterol-Dependent Nanomechanical Stability of Phase-Segregated Multicomponent Lipid Bilayers
journal, July 2010


Impact of lithiated cobalt oxide and phosphate nanoparticles on rainbow trout gill epithelial cells
journal, November 2018


Quaternary Amine-Terminated Quantum Dots Induce Structural Changes to Supported Lipid Bilayers
journal, September 2018


Poly-L-Lysine-Induced Morphology Changes in Mixed Anionic/Zwitterionic and Neat Zwitterionic-Supported Phospholipid Bilayers
journal, October 2006


Interactions of Poly(amidoamine) Dendrimers with Survanta Lung Surfactant: The Importance of Lipid Domains
journal, October 2008

  • Erickson, Blake; DiMaggio, Stassi C.; Mullen, Douglas G.
  • Langmuir, Vol. 24, Issue 19
  • DOI: 10.1021/la801497d

Effects of Ceramide on Liquid-Ordered Domains Investigated by Simultaneous AFM and FCS
journal, June 2006


Expression of GM1, a marker of lipid rafts, defines two subsets of human monocytes with differential endocytic capacity and lipopolysaccharide responsiveness
journal, April 2007

  • Moreno-Altamirano, M. Maximina Bertha; Aguilar-Carmona, Israel; Sánchez-García, F. Javier
  • Immunology, Vol. 120, Issue 4
  • DOI: 10.1111/j.1365-2567.2006.02531.x

Physical Principles of Nanoparticle Cellular Endocytosis
journal, August 2015


High-Resolution Correlative Microscopy: Bridging the Gap between Single Molecule Localization Microscopy and Atomic Force Microscopy
journal, July 2015


Progress in the Correlative Atomic Force Microscopy and Optical Microscopy
journal, April 2017

  • Zhou, Lulu; Cai, Mingjun; Tong, Ti
  • Sensors, Vol. 17, Issue 4
  • DOI: 10.3390/s17040938

Clathrin to Lipid Raft-Endocytosis via Controlled Surface Chemistry and Efficient Perinuclear Targeting of Nanoparticle
journal, August 2015


The interaction of lipid-liganded gold clusters (Aurora ™) with lipid bilayers
journal, January 2019


Nanoparticle Adhesion to the Cell Membrane and Its Effect on Nanoparticle Uptake Efficiency
journal, January 2013

  • Lesniak, Anna; Salvati, Anna; Santos-Martinez, Maria J.
  • Journal of the American Chemical Society, Vol. 135, Issue 4
  • DOI: 10.1021/ja309812z

The mystery of membrane organization: composition, regulation and roles of lipid rafts
journal, March 2017

  • Sezgin, Erdinc; Levental, Ilya; Mayor, Satyajit
  • Nature Reviews Molecular Cell Biology, Vol. 18, Issue 6
  • DOI: 10.1038/nrm.2017.16

Cell Membranes Open “Doors” for Cationic Nanoparticles/Biomolecules: Insights into Uptake Kinetics
journal, November 2013

  • Lin, Jiaqi; Alexander-Katz, Alfredo
  • ACS Nano, Vol. 7, Issue 12
  • DOI: 10.1021/nn4040553

The multi-tasked life of GM1 ganglioside, a true factotum of nature
journal, July 2015


Physicochemical Properties Determine Nanomaterial Cellular Uptake, Transport, and Fate
journal, July 2012

  • Zhu, Motao; Nie, Guangjun; Meng, Huan
  • Accounts of Chemical Research, Vol. 46, Issue 3
  • DOI: 10.1021/ar300031y

Wide Varieties of Cationic Nanoparticles Induce Defects in Supported Lipid Bilayers
journal, January 2008

  • Leroueil, Pascale R.; Berry, Stephanie A.; Duthie, Kristen
  • Nano Letters, Vol. 8, Issue 2
  • DOI: 10.1021/nl0722929

DNA Nanostructure-Programmed Like-Charge Attraction at the Cell-Membrane Interface
journal, September 2018


Biological Responses to Engineered Nanomaterials: Needs for the Next Decade
journal, June 2015

  • Murphy, Catherine J.; Vartanian, Ariane M.; Geiger, Franz M.
  • ACS Central Science, Vol. 1, Issue 3
  • DOI: 10.1021/acscentsci.5b00182

Lipopolysaccharide Density and Structure Govern the Extent and Distance of Nanoparticle Interaction with Actual and Model Bacterial Outer Membranes
journal, August 2015

  • Jacobson, Kurt H.; Gunsolus, Ian L.; Kuech, Thomas R.
  • Environmental Science & Technology, Vol. 49, Issue 17
  • DOI: 10.1021/acs.est.5b01841

Gill cell culture systems as models for aquatic environmental monitoring
journal, February 2014

  • Bury, N. R.; Schnell, S.; Hogstrand, C.
  • Journal of Experimental Biology, Vol. 217, Issue 5
  • DOI: 10.1242/jeb.095430

Line tension at lipid phase boundaries as driving force for HIV fusion peptide-mediated fusion
journal, April 2016

  • Yang, Sung-Tae; Kiessling, Volker; Tamm, Lukas K.
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms11401

Preparation of DOPC and DPPC Supported Planar Lipid Bilayers for Atomic Force Microscopy and Atomic Force Spectroscopy
journal, February 2013

  • Attwood, Simon; Choi, Youngjik; Leonenko, Zoya
  • International Journal of Molecular Sciences, Vol. 14, Issue 2
  • DOI: 10.3390/ijms14023514

Fiji: an open-source platform for biological-image analysis
journal, June 2012

  • Schindelin, Johannes; Arganda-Carreras, Ignacio; Frise, Erwin
  • Nature Methods, Vol. 9, Issue 7
  • DOI: 10.1038/nmeth.2019

Continuous Flow Atomic Force Microscopy Imaging Reveals Fluidity and Time-Dependent Interactions of Antimicrobial Dendrimer with Model Lipid Membranes
journal, December 2013

  • Lind, Tania Kjellerup; Zielińska, Paulina; Wacklin, Hanna Pauliina
  • ACS Nano, Vol. 8, Issue 1
  • DOI: 10.1021/nn404530z

Quantum dots: from fluorescence to chemiluminescence, bioluminescence, electrochemiluminescence, and electrochemistry
journal, January 2017


Evaluation of fluorophores for optimal performance in localization-based super-resolution imaging
journal, November 2011

  • Dempsey, Graham T.; Vaughan, Joshua C.; Chen, Kok Hao
  • Nature Methods, Vol. 8, Issue 12
  • DOI: 10.1038/nmeth.1768

Lipid phase influences the binding of Bacillus thuringiensis Cyt2Aa2 toxin on model lipid membranes
journal, April 2019

  • Tharad, Sudarat; Promdonkoy, Boonhiang; Toca-Herrera, José L.
  • Biochemical and Biophysical Research Communications, Vol. 511, Issue 2
  • DOI: 10.1016/j.bbrc.2019.02.072

ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging
journal, May 2014


Functional rafts in cell membranes
journal, June 1997

  • Simons, Kai; Ikonen, Elina
  • Nature, Vol. 387, Issue 6633
  • DOI: 10.1038/42408

Peripheral Membrane Proteins Facilitate Nanoparticle Binding at Lipid Bilayer Interfaces
journal, August 2018


HIV gp41–mediated membrane fusion occurs at edges of cholesterol-rich lipid domains
journal, April 2015

  • Yang, Sung-Tae; Kiessling, Volker; Simmons, James A.
  • Nature Chemical Biology, Vol. 11, Issue 6
  • DOI: 10.1038/nchembio.1800

Cellular uptake of nanoparticles: journey inside the cell
journal, January 2017

  • Behzadi, Shahed; Serpooshan, Vahid; Tao, Wei
  • Chemical Society Reviews, Vol. 46, Issue 14
  • DOI: 10.1039/C6CS00636A

Curvature-driven adsorption of cationic nanoparticles to phase boundaries in multicomponent lipid bilayers
journal, January 2019

  • Sheavly, Jonathan K.; Pedersen, Joel A.; Van Lehn, Reid C.
  • Nanoscale, Vol. 11, Issue 6
  • DOI: 10.1039/C8NR07763K

Tracking microdomain dynamics in cell membranes
journal, January 2009

  • Day, Charles A.; Kenworthy, Anne K.
  • Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1788, Issue 1
  • DOI: 10.1016/j.bbamem.2008.10.024

A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors
journal, February 2006

  • Hardman, Ron
  • Environmental Health Perspectives, Vol. 114, Issue 2
  • DOI: 10.1289/ehp.8284

Boundary region between coexisting lipid phases as initial binding sites for Escherichia coli alpha-hemolysin: A real-time study
journal, July 2014

  • Maté, Sabina M.; Vázquez, Romina F.; Herlax, Vanesa S.
  • Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1838, Issue 7
  • DOI: 10.1016/j.bbamem.2014.02.022

Phospholipid Composition Modulates Carbon Nanodiamond-Induced Alterations in Phospholipid Domain Formation
journal, April 2015

  • Chakraborty, Aishik; Mucci, Nicolas J.; Tan, Ming Li
  • Langmuir, Vol. 31, Issue 18
  • DOI: 10.1021/la504923j

Aggregation of nanoparticles on one and two-component bilayer membranes
journal, November 2014

  • Cheung, David L.
  • The Journal of Chemical Physics, Vol. 141, Issue 19
  • DOI: 10.1063/1.4901740

Synthetic and Natural Polycationic Polymer Nanoparticles Interact Selectively with Fluid-Phase Domains of DMPC Lipid Bilayers
journal, September 2005

  • Mecke, Almut; Lee, Dong-Kuk; Ramamoorthy, Ayyalusamy
  • Langmuir, Vol. 21, Issue 19
  • DOI: 10.1021/la051800w