Our study demonstrates that nanoplasmonic sensing (NPS) can be utilized for the determination of the phase transition temperature (Tm) of phospholipids. During the phase transition, the lipid bilayer undergoes a conformational change. Therefore, it is presumed that the Tm of phospholipids can be determined by detecting conformational changes in liposomes. The studied lipids included 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Liposomes in gel phase are immobilized onto silicon dioxide sensors and the sensor cell temperature is increased until passing the Tm of the lipid. The results show that, when the system temperature approaches the Tm, a drop of the NPS signal is observed. The breakpoints in the temperatures are 22.5 °C, 41.0 °C, and 55.5 °C for DMPC, DPPC, and DSPC, respectively. These values are very close to the theoretical Tm values, i.e., 24 °C, 41.4 °C, and 55 °C for DMPC, DPPC, and DSPC, respectively. Our studies prove that the NPS methodology is a simple and valuable tool for the determination of the Tm of phospholipids.

Department of Bioproducts and Biosystems POB 16300 00076 Aalto University Espoo Finland

Department of Chemistry POB 55 00014 University of Helsinki Helsinki Finland

Institute of Analytical Chemistry of the Czech Academy of Sciences Veveří 97 Brno 60200 Czech Republic

Zobrazit více v PubMed

Singer S, Nicolson G. The fluid mosaic model of the structure of cell membranes. Science. 1972;175:720–731. doi: 10.1126/science.175.4023.720. PubMed DOI

Eeman M, Deleu M. From biological membranes to biomimetic model membranes. Biotechnol. Agron. Soc. 2010;14:719–736.

Mozsolits H, Lee T, Wirth H, Perlmutter P, Aguilar M. The interaction of bioactive peptides with an immobilized phosphatidylcholine monolayer. Biophys. J. 1999;77:1428–1444. doi: 10.1016/S0006-3495(99)76991-2. PubMed DOI PMC

Hu W, et al. Use of a biomimetic chromatographic stationary phase for study of the interactions occurring between inorganic anions and phosphatidylcholine membranes. Biophys. J. 2002;83:3351–3356. doi: 10.1016/S0006-3495(02)75335-6. PubMed DOI PMC

Gabriel GJ, et al. Interactions between antimicrobial polynorbornenes and phospholipid vesicles monitored by light scattering and microcalorimetry. Langmuir. 2008;24:12489–12495. doi: 10.1021/la802232p. PubMed DOI

Fan R, et al. An interaction of helicid with liposome biomembrane. Appl. Surf. Sci. 2011;257:2102–2106. doi: 10.1016/j.apsusc.2010.09.057. DOI

Lian T, Ho RJY. Trends and developments in liposome drug delivery systems. J. Pharm. Sci. 2001;90:667–680. doi: 10.1002/jps.1023. PubMed DOI

Needham D, Anyarambhatla G, Kong G, Dewhirst MW. A new temperature-sensitive liposome for use with mild hyperthermia: Characterization and testing in a human tumor xenograft model. Cancer Res. 2000;60:1197–1201. PubMed

Koynova R, MacDonald RC. Cationic o-ethylphosphatidylcholines and their lipoplexes: phase behavior aspects, structural organization and morphology. BBA-Biomembranes. 2003;1613:39–48. doi: 10.1016/S0005-2736(03)00135-4. PubMed DOI

Landon CD, Park J, Needham D, Dewhirst MW. Nanoscale drug delivery and hyperthermia: The materials design and preclinical and clinical testing of low temperature-sensitive liposomes used in combination with mild hyperthermia in the treatment of local cancer. Open Nanomed. J. 2011;3:38–64. doi: 10.2174/1875933501103010038. PubMed DOI PMC

Park SM, et al. Novel temperature-triggered liposome with high stability: Formulation, in vitro evaluation, and in vivo study combined with high-intensity focused ultrasound (HIFU) J. Controlled Release. 2013;170:373–379. doi: 10.1016/j.jconrel.2013.06.003. PubMed DOI

Kneidl B, Peller M, Winter G, Lindner LH, Hossann M. Thermosensitive liposomal drug delivery systems: state of the art review. Int. J. Nanomed. 2014;9:4387–4398. PubMed PMC

Kinnunen PKJ. On the principles of functional ordering in biological membranes. Chem. Phys. Lipids. 1991;57:375–399. doi: 10.1016/0009-3084(91)90087-R. PubMed DOI

Noothalapati H, et al. Imaging phospholipid conformational disorder and packing in giant multilamellar liposome by confocal Raman microspectroscopy. Spectroc. Acta Pt. A-Molec. Biomolec. Spectr. 2017;187:186–190. doi: 10.1016/j.saa.2017.06.060. PubMed DOI

Oh E, et al. Contribution of temperature to deformation of adsorbed vesicles studied by nanoplasmonic biosensing. Langmuir. 2015;31:771–781. doi: 10.1021/la504267g. PubMed DOI

Jacobson K, Papahadjopoulos D. Phase-transitions and phase separations in phospholipid membranes induced by changes in temperature, pH, and concentration of bivalent-cations. Biochemistry. 1975;14:152–161. doi: 10.1021/bi00672a026. PubMed DOI

Suurkuusk J, Lentz BR, Barenholz Y, Biltonen RL, Thompson TE. Calorimetric and fluorescent-probe study of gel-liquid crystalline phase-transition in small, single-lamellar dipalmitoylphosphatidylcholine vesicles. Biochemistry. 1976;15:1393–1401. doi: 10.1021/bi00652a007. PubMed DOI

Biltonen R, Lichtenberg D. The use of differential scanning calorimetry as a tool to characterize liposome preparations. Chem. Phys. Lipids. 1993;64:129–142. doi: 10.1016/0009-3084(93)90062-8. DOI

Chiu MH, Prenner EJ. Differential scanning calorimetry: An invaluable tool for a detailed thermodynamic characterization of macromolecules and their interactions. J. Pharm. Bioallied Sci. 2011;3:39–59. doi: 10.4103/0975-7406.76463. PubMed DOI PMC

Papahadjopoulos D, Jacobson K, Nir S, Isac T. Phase-transitions in phospholipid vesicles - fluorescence polarization and permeability measurements concerning effect of temperature and cholesterol. Biochim. Biophys. Acta. 1973;311:330–348. doi: 10.1016/0005-2736(73)90314-3. PubMed DOI

Schaefer JJ, Ma C, Harris JM. Confocal raman microscopy probing of temperature-controlled release from individual, optically-trapped phospholipid vesicles. Anal. Chem. 2012;84:9505–9512. doi: 10.1021/ac302346n. PubMed DOI

Chen J, et al. Influence of lipid composition on the phase transition temperature of liposomes composed of both DPPC and HSPC. Drug Dev. Ind. Pharm. 2013;39:197–204. doi: 10.3109/03639045.2012.668912. PubMed DOI

Cho N, Jackman JA, Liu M, Frank CW. pH-Driven assembly of various supported lipid platforms: A comparative study on silicon oxide and titanium oxide. Langmuir. 2011;27:3739–3748. doi: 10.1021/la104348f. PubMed DOI

Duša F, Ruokonen S, Petrovaj J, Viitala T, Wiedmer SK. Ionic liquids affect the adsorption of liposomes onto cationic polyelectrolyte coated silica evidenced by quartz crystal microbalance. Colloid Surf. B-Biointerfaces. 2015;136:496–505. doi: 10.1016/j.colsurfb.2015.09.059. PubMed DOI

Hasan IY, Mechler A. Nanoviscosity measurements revealing domain formation in biomimetic membranes. Anal. Chem. 2017;89:1855–1862. doi: 10.1021/acs.analchem.6b04256. PubMed DOI

Jonsson MP, Jönsson P, Dahlin AB, Höök F. Supported lipid bilayer formation and lipid-membrane-mediated biorecognition reactions studied with a new nanoplasmonic sensor template. Nano Lett. 2007;7:3462–3468. doi: 10.1021/nl072006t. PubMed DOI

Höök F, et al. Supported lipid bilayers, tethered lipid vesicles, and vesicle fusion investigated using gravimetric, plasmonic, and microscopy techniques. Biointerphases. 2008;3:FA108–FA116. doi: 10.1116/1.2948313. PubMed DOI

Jonsson MP, Jönsson P, Höök F. Simultaneous nanoplasmonic and quartz crystal microbalance sensing: Analysis of biomolecular conformational changes and quantification of the bound molecular mass. Anal. Chem. 2008;80:7988–7995. doi: 10.1021/ac8008753. PubMed DOI

Bruzas I, Unser S, Yazdi S, Ringe E, Sagle L. Ultrasensitive plasmonic platform for label-free detection of membrane-associated species. Anal. Chem. 2016;88:7968–7974. doi: 10.1021/acs.analchem.6b00801. PubMed DOI

Dacic M, et al. Influence of divalent cations on deformation and rupture of adsorbed lipid vesicles. Langmuir. 2016;32:6486–6495. doi: 10.1021/acs.langmuir.6b00439. PubMed DOI

Ferhan AR, Jackman JA, Cho N. Integration of quartz crystal microbalance-dissipation and reflection-mode localized surface plasmon resonance sensors for biomacromolecular interaction analysis. Anal. Chem. 2016;88:12524–12531. doi: 10.1021/acs.analchem.6b04303. PubMed DOI

Ferhan AR, Jackman JA, Cho N. Probing spatial proximity of supported lipid bilayers to silica surfaces by localized surface plasmon resonance sensing. Anal. Chem. 2017;89:4301–4308. doi: 10.1021/acs.analchem.7b00370. PubMed DOI

Russo G, Witos J, Rantamäki AH, Wiedmer SK. Cholesterol affects the interaction between an ionic liquid and phospholipid vesicles. A study by differential scanning calorimetry and nanoplasmonic sensing. BBA-Biomembranes. 2017;1859:2361–2372. doi: 10.1016/j.bbamem.2017.09.011. PubMed DOI

Jackman JA, et al. Quantitative profiling of nanoscale liposome deformation by a localized surface plasmon resonance sensor. Anal. Chem. 2017;89:1102–1109. doi: 10.1021/acs.analchem.6b02532. PubMed DOI

Ohlsson G, Tigerstrom A, Höök F, Kasemo B. Phase transitions in adsorbed lipid vesicles measured using a quartz crystal microbalance with dissipation monitoring. Soft Matter. 2011;7:10749–10755. doi: 10.1039/c1sm05923h. DOI

Seantier B, Breffa C, Félix O, Decher G. In situ investigations of the formation of mixed supported lipid bilayers close to the phase transition temperature. Nano Lett. 2004;4:5–10. doi: 10.1021/nl034590l. DOI

Wargenau A, Tufenkji N. Direct detection of the gel-fluid phase transition of a single supported phospholipid bilayer using quartz crystal microbalance with dissipation monitoring. Anal. Chem. 2014;86:8017–8020. doi: 10.1021/ac5019183. PubMed DOI

Peschel A, et al. Lipid phase behavior studied with a quartz crystal microbalance: A technique for biophysical studies with applications in screening. J. Chem. Phys. 2016;145:204904. doi: 10.1063/1.4968215. PubMed DOI

Losada-Pérez P, et al. Phase transitions in lipid vesicles detected by a complementary set of methods: heat-transfer measurements, adiabatic scanning calorimetry, and dissipation-mode quartz crystal microbalance. Phys. Status Solidi A-Appl. Mat. 2014;211:1377–1388. doi: 10.1002/pssa.201431060. DOI

Losada-Pérez P, Khorshid M, Yongabi D, Wagner P. Effect of cholesterol on the phase behavior of solid-supported lipid vesicle layers. J. Phys. Chem. B. 2015;119:4985–4992. doi: 10.1021/acs.jpcb.5b00712. PubMed DOI

Losada-Pérez, P.

Jackman JA, et al. Indirect nanoplasmonic sensing platform for monitoring temperature-dependent protein adsorption. Anal. Chem. 2017;89:12976–12983. doi: 10.1021/acs.analchem.7b03921. PubMed DOI

Willets KA, Van Duyne RP. Localized surface plasmon resonance spectroscopy and sensing. Annu. Rev. Phys. Chem. 2007;58:267–297. doi: 10.1146/annurev.physchem.58.032806.104607. PubMed DOI

Anker JN, et al. Biosensing with plasmonic nanosensors. Nat. Mater. 2008;7:442–453. doi: 10.1038/nmat2162. PubMed DOI

Langhammer C, Larsson EM, Kasemo B, Zorić I. Indirect nanoplasmonic sensing: Ultrasensitive experimental platform for nanomaterials science and optical nanocalorimetry. Nano Lett. 2010;10:3529–3538. doi: 10.1021/nl101727b. PubMed DOI

Larsson EM, Syrenova S, Langhammer C. Nanoplasmonic sensing for nanomaterials science. Nanophotonics. 2012;1:249–266. doi: 10.1515/nanoph-2012-0029. DOI

Mazzotta F, et al. Influence of the evanescent field decay length on the sensitivity of plasmonic nanodisks and nanoholes. ACS Photonics. 2015;2:256–262. doi: 10.1021/ph500360d. DOI

Seifert U, Lipowsky R. Adhesion of vesicles. Phys. Rev. A. 1990;42:4768–4771. doi: 10.1103/PhysRevA.42.4768. PubMed DOI

Seifert U. Configurations of fluid membranes and vesicles. Adv. Phys. 1997;46:13–137. doi: 10.1080/00018739700101488. DOI

Witos J, Russo G, Ruokonen S, Wiedmer SK. Unraveling interactions between ionic liquids and phospholipid vesicles using nanoplasmonic sensing. Langmuir. 2017;33:1066–1076. doi: 10.1021/acs.langmuir.6b04359. PubMed DOI

Jackman JA, Zhdanov VP, Cho N. Nanoplasmonic biosensing for soft matter adsorption: kinetics of lipid vesicle attachment and shape deformation. Langmuir. 2014;30:9494–9503. doi: 10.1021/la502431x. PubMed DOI

Jackman JA, et al. Nanoplasmonic ruler to measure lipid vesicle deformation. Chem. Commun. 2016;52:76–79. doi: 10.1039/C5CC06861D. PubMed DOI

Diggins P, McDargh ZA, Deserno M. Curvature softening and negative compressibility of gel-ahase lipid membranes. J. Am. Chem. Soc. 2015;137:12752–12755. doi: 10.1021/jacs.5b06800. PubMed DOI

Leonenko ZV, Finot E, Ma H, Dahms TES, Cramb DT. Investigation of temperature-induced phase transitions in DOPC and DPPC phospholipid bilayers using temperature-controlled scanning force microscopy. Biophys. J. 2004;86:3783–3793. doi: 10.1529/biophysj.103.036681. PubMed DOI PMC

Lichtenberg D, Schmidt CF, Barenholz Y, Felgner PL, Thompson TE. Effect of surface curvature on stability, thermodynamic behavior, and osmotic activity of dipalmitoylphosphatidylcholine single lamellar vesicles. Biochemistry. 1981;20:3462–3467. doi: 10.1021/bi00515a024. PubMed DOI

Drazenovic J, et al. Effect of lamellarity and size on calorimetric phase transitions in single component phosphatidylcholine vesicles. BBA-Biomembranes. 2015;1848:532–543. doi: 10.1016/j.bbamem.2014.10.003. PubMed DOI

Mabrey S, Sturtevant JM. Investigation of phase-transitions of lipids and lipid mixtures by high sensitivity differential scanning calorimetry. Proc. Natl. Acad. Sci. USA. 1976;73:3862–3866. doi: 10.1073/pnas.73.11.3862. PubMed DOI PMC

Lentz BR, Freire E, Biltonen RL. Fluorescence and calorimetric studies of phase-transitions in phosphatidylcholine multilayers - kinetics of pretransition. Biochemistry. 1978;17:4475–4480. doi: 10.1021/bi00614a018. PubMed DOI

Perkins W, et al. Solute-induced shift of phase transition temperature in Di-saturated PC liposomes: Adoption of ripple phase creates osmotic stress. BBA-Biomembranes. 1997;1327:41–51. doi: 10.1016/S0005-2736(97)00042-4. PubMed DOI

Ali S, Minchey S, Janoff A, Mayhew E. A differential scanning calorimetry study of phosphocholines mixed with paclitaxel and its bromoacylated taxanes. Biophys. J. 2000;78:246–256. doi: 10.1016/S0006-3495(00)76588-X. PubMed DOI PMC

López O, et al. Direct formation of mixed micelles in the solubilization of phospholipid liposomes by Triton X-100. FEBS Lett. 1998;426:314–318. doi: 10.1016/S0014-5793(98)00363-9. PubMed DOI

Lichtenberg D, Ahyayauch H, Alonso A, Goñi FM. Detergent solubilization of lipid bilayers: a balance of driving forces. Trends Biochem. Sci. 2013;38:85–93. doi: 10.1016/j.tibs.2012.11.005. PubMed DOI

Wiedmer SK, Holopainen JM, Mustakangas P, Kinnunen PKJ, Riekkola ML. Liposomes as carriers in electrokinetic capillary chromatography. Electrophoresis. 2000;21:3191–3198. doi: 10.1002/1522-2683(20000901)21:15<3191::AID-ELPS3191>3.0.CO;2-J. PubMed DOI

Wesołowska O, Kużdżał M, Štrancar J, Michalak K. Interaction of the chemopreventive agent resveratrol and its metabolite, piceatannol, with model membranes. BBA-Biomembranes. 2009;1788:1851–1860. doi: 10.1016/j.bbamem.2009.06.005. PubMed DOI

Rantamäki AH, et al. Impact of surface-active guanidinium-, tetramethylguanidinium-, and cholinium-based ionic liquids on vibrio fischeri cells and dipalmitoylphosphatidylcholine liposomes. Sci. Rep. 2017;7:46673. doi: 10.1038/srep46673. PubMed DOI PMC

Holding AJ, Heikkilä M, Kilpeläinen I, King AWT. Amphiphilic and phase-separable ionic liquids for biomass processing. ChemSusChem. 2014;7:1422–1434. doi: 10.1002/cssc.201301261. PubMed DOI