Abstract
A synthetic protocol is described for preparing lipid-coated gold nanoparticles (AuNPs) of varying shape, size, and membrane composition. Using ultraviolet-visible spectroscopy (UV-Vis), the localized surface plasmon resonance (LSPR) of the AuNPs is used to examine nanoparticle stability. Highly spherical AuNPs are obtained by selectively etching octahedral nanoparticles with cyanide. Alkanethiols are used to anchor the membranes to the gold surface, creating hybrid lipid membranes. Cyanide etch studies are described that test membrane stability and coverage and are performed by monitoring changes to the LSPR. A strategy is provided for minimizing the amounts of excess lipids and thiols present while using minimal purification steps. The design strategy can be used to produce a library of stable, hybrid lipid-coated AuNPs for applications including drug delivery, imaging, and sensing. Methods for using these AuNPs to study protein-membrane interactions using UV-Vis spectroscopy and dynamic light-scattering (DLS) measurements are also described.
Keywords
- Beta amyloid (Aβ) peptides
- C-reactive protein
- Gold nanoparticles
- Hybrid membranes
- Protein-membrane interactions
- Sensors
These authors contributed equally to the work.
This is a preview of subscription content, access via your institution.
Buying options






References
Tanaka M, Sackmann E (2005) Polymer-supported membranes as models of the cell surface. Nature 437(7059):656–663. doi:10.1038/nature04164
Plant AL (1999) Supported hybrid bilayer membranes as rugged cell membrane mimics. Langmuir 15(15):5128–5135. doi:10.1021/la981662t
Baksh MM, Jaros M, Groves JT (2004) Detection of molecular interactions at membrane surfaces through colloid phase transitions. Nature 427(6970):139–141. doi:10.1038/nature02209
Mackiewicz MR, Ayres BR, Reed SM (2008) Reversible, reagentless solubility changes in phosphatidylcholine-stabilized gold nanoparticles. Nanotechnology 19:115607. doi: 10.1088/0957-4484/19/11/115607
Brust M, Walker M, Bethell D, Schiffrin DJ, Whyman R (1994) Synthesis of thiol-derivatised gold nanoparticles in a two-phase liquid-liquid system. J Chem Soc Chem Commun 7:801–802. doi:10.1039/c39940000801
Hong K, Friend DS, Glabe CG, Papahadjopoulos D (1983) Liposomes containing colloidal gold are a useful probe of liposome-cell interactions. Biochim Biophys Acta 732(1):320–323. doi:10.1016/0005-2736(83)90220-1
Chhour P, Naha PC, O’Neill SM, Litt HI, Reilly MP, Ferrari VA, Cormode DP (2016) Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography. Biomaterials 87:93–103. doi: 10.1016/j.biomaterials.2016.02.009
Kang JH, Ko YT (2015) Lipid-coated gold nanocomposites for enhanced cancer therapy. Int J Nanomed 10 Spec Iss:33–45. doi: 10.2147/IJN.S88307
Boisselier E, Astruc D (2009) Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev 38(6):1759–1782. doi: 10.1039/b806051g
Sackmann E (1996) Supported membranes: scientific and practical applications. Science 271(5245):43–48. doi: 10.1126/science.271.5245.43
Groves JT, Boxer SG (2002) Micropattern formation in supported lipid membranes. Acc Chem Res 35(3):149–157. doi:10.1021/ar950039m
Lahiri J, Kalal P, Frutos AG, Jonas SJ, Schaeffler R (2000) Method for fabricating supported bilayer lipid membranes on gold. Langmuir 16(20):7805–7810. doi:10.1021/la000468f
Love JC, Estroff LA, Kriebel JK, Nuzzo RG, Whitesides GM (2005) Self-assembled monolayers of thiolates on metals as a form of nanotechnology. Chem Rev 105(4):1103–1170. doi:10.1021/cr0300789
Wang MS, Messersmith RE, Reed SM (2012) Membrane curvature recognition by C-reactive protein using lipoprotein mimics. Soft Matter 8(30):7909–7918. doi:10.1039/c2sm25779c
He P, Urban MW (2005) Phospholipid-stabilized Au−nanoparticles. Biomacromolecules 6(3):1224–1225. doi:10.1021/bm0501961
Robertson D, Tiersch B, Kosmella S, Koetz J (2007) Preparation of crystalline gold nanoparticles at the surface of mixed phosphatidylcholine-ionic surfactant vesicles. J Colloid Interface Sci 305(2):345–351. doi:10.1016/j.jcis.2006.09.079
Marie-Edith M, Olivier L, Bernard D, Chrystel F (2006) Synthesis of stable, gold-particle-containing onion-type multilamellar vesicles. Influence of particle size on the onions’ internal structure. Nanotechnology 17(5):1193. doi:10.1088/0957-4484/17/5/005
He P, Zhu X (2007) Phospholipid-assisted synthesis of size-controlled gold nanoparticles. Mater Res Bull 42(7):1310–1315. doi:10.1016/j.materresbull.2006.10.014
Levin CS, Kundu J, Janesko BG, Scuseria GE, Raphael RM, Halas NJ (2008) Interactions of ibuprofen with hybrid lipid bilayers probed by complementary surface-enhanced vibrational spectroscopies. J Phys Chem B 112(45):14168–14175. doi:10.1021/jp804374e
Mackiewicz MR, Hodges HL, Reed SM (2010) C-Reactive protein induced rearrangement of phosphatidylcholine on nanoparticle mimics of lipoprotein particles. J Phys Chem B 114(16):5556–5562. doi:10.1021/jp911617q
Knoll W, Köper I, Naumann R, Sinner E-K (2008) Tethered bimolecular lipid membranes—a novel model membrane platform. Electrochim Acta 53(23):6680–6689. doi:10.1016/j.electacta.2008.02.121
Yang JA, Murphy CJ (2012) Evidence for patchy lipid layers on gold nanoparticle surfaces. Langmuir 28(12):5404–5416. doi:10.1021/la300325p
Sitaula S, Mackiewicz MR, Reed SM (2008) Gold nanoparticles become stable to cyanide etch when coated with hybrid lipid bilayers. Chem Commun 26:3013–3015. doi: 10.1039/B801525B
Brown LO, Hutchison JE (2001) Formation and electron diffraction studies of ordered 2-D and 3-D superlattices of amine-stabilized gold nanocrystals. J Phys Chem B 105(37):8911–8916. doi:10.1021/jp011231a
Turkevich J, Stevenson PC, Hillier J (1951) A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss Faraday Soc 11:55–75. doi:10.1039/df9511100055
Chen H, Kou X, Yang Z, Ni W, Wang J (2008) Shape- and size-dependent refractive index sensitivity of gold nanoparticles. Langmuir 24(10):5233–5237. doi:10.1021/la800305j
Ayres BR, Reed SM (2014) A minor lipid component of soy lecithin causes growth of triangular prismatic gold nanoparticles. Environ Sci Nano 1(1):37–44. doi:10.1039/c3en00015j
Lee Y-J, Schade NB, Sun L, Fan JA, Bae DR, Mariscal MM, Lee G, Capasso F, Sacanna S, Manoharan VN, Yi G-R (2013) Ultrasmooth, highly spherical monocrystalline gold particles for precision plasmonics. ACS Nano 7(12):11064–11070. doi:10.1021/nn404765w
Li C, Shuford KL, Chen M, Lee EJ, Cho SO (2008) A facile polyol route to uniform gold octahedra with tailorable size and their optical properties. ACS Nano 2(9):1760–1769. doi:10.1021/nn800264q
Ji X, Song X, Li J, Bai Y, Yang W, Peng X (2007) Size control of gold nanocrystals in citrate reduction: the third role of citrate. J Am Chem Soc 129(45):13939–13948. doi:10.1021/ja074447k
Thurmond RL, Dodd SW, Brown MF (1991) Molecular areas of phospholipids as determined by 2H NMR spectroscopy. Comparison of phosphatidylethanolamines and phosphatidylcholines. Biophys J 59(1):108–113. doi:10.1016/S0006-3495(91)82203-2
Nagle JF, Tristram-Nagle S (2000) Lipid bilayer structure. Curr Opin Struct Biol 10(4):474–480
Messersmith RE, Nusz GJ, Reed SM (2013) Using the localized surface plasmon resonance of gold nanoparticles to monitor lipid membrane assembly and protein binding. J Phys Chem C 117(50):26725–26733. doi:10.1021/jp406013q
Haiss W, Thanh NTK, Aveyard J, Fernig DG (2007) Determination of size and concentration of gold nanoparticles from UV−Vis spectra. Anal Chem 79(11):4215–4221. doi:10.1021/ac0702084
Ridker PM, Hennekens CH, Buring JE, Rifai N (2000) C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342(12):836–843. doi: 10.1056/NEJM200003233421202
Shrive AK, Cheetham GM, Holden D, Myles DA, Turnell WG, Volanakis JE, Pepys MB, Bloomer AC, Greenhough TJ (1996) Three dimensional structure of human C-reactive protein. Nat Struct Biol 3(4):346–354. doi:10.1038/nsb0496-346
Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest 111(12):1805–1812. doi:10.1172/JCI18921
Fu T, Borensztajn J (2002) Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: possible mechanism of foam-cell formation in atherosclerotic lesions. Biochem J 366(Pt 1):195–201. doi:10.1042/BJ20020045
Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, Ashe KH (2005) Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat Neurosci 8(1):79–84 doi:10.1038/nn1372
Gong Y, Chang L, Viola KL, Lacor PN, Lambert MP, Finch CE, Krafft GA, Klein WL (2003) Alzheimer’s disease-affected brain: presence of oligomeric Aβ ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc Natl Acad Sci 100(18):10417–10422. doi:10.1073/pnas.1834302100
Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL (1998) Diffusible, nonfibrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins. Proc Natl Acad Sci 95(11):6448–6453
Walsh DM, Klyubin I, Fadeeva JV, Rowan MJ, Selkoe DJ (2002) Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition. Biochem Soc Trans 30(4):552–557. doi: 10.1042/bst0300552
Wong PT, Schauerte JA, Wisser KC, Ding H, Lee EL, Steel DG, Gafni A (2009) Amyloid-β membrane binding and permeabilization are distinct processes influenced separately by membrane charge and fluidity. J Mol Biol 386(1):81–96. doi:10.1016/j.jmb.2008.11.060
Jang H, Zheng J, Lal R, Nussinov R (2008) New structures help the modeling of toxic amyloidbeta ion channels. Trends Biochem Sci 33(2):91–100. doi:10.1016/j.tibs.2007.10.007
Berthelot K, Cullin C, Lecomte S (2012) What does make an amyloid toxic: morphology, structure or interaction with membrane? Biochimie 20:20. doi: 10.1016/j.biochi.2012.07.011
Williams TL, Serpell LC (2011) Membrane and surface interactions of Alzheimer’s Abeta peptide—insights into the mechanism of cytotoxicity. FEBS J 278(20):3905–3917. doi: 10.1111/j.1742-4658.2011.08228.x
Abramov AY, Ionov M, Pavlov E, Duchen MR (2011) Membrane cholesterol content plays a key role in the neurotoxicity of β-amyloid: implications for Alzheimer’s disease. Aging Cell 10(4):595–603. doi:10.1111/j.1474-9726.2011.00685.x
Acknowledgments
This work was supported by a grant from the NIH (2R15GM088960-02) (to SMR) and the Collins Medical Trust (to MMR). We thank the Electron Microscopy Center in the University of Colorado Anschutz Medical Campus School of Medicine and Dorothy Dill for assistance in running the TEM. Support from The Wenner-Gren Foundation for SMR is acknowledged. We also appreciate input from many group members that assisted in the development of these protocols over many years including Min Wang, Heather Hodges, Reid Messersmith, and Benjamin Ayres.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Hamilton, D.J., Cai, Y., Kaur, R., Marquart, G.W., Mackiewicz, M.R., Reed, S.M. (2016). Lipid-Coated Gold Nanoparticles as Probes for Membrane Binding. In: Shukla, A. (eds) Chemical and Synthetic Approaches in Membrane Biology. Springer Protocols Handbooks. Humana Press, New York, NY. https://doi.org/10.1007/8623_2016_8
Download citation
DOI: https://doi.org/10.1007/8623_2016_8
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-6835-0
Online ISBN: 978-1-4939-6836-7
eBook Packages: Springer Protocols
