Plasma membranes as well as their simplified model systems show an inherent nanoscale heterogeneity. As a result of strong interleaflet interactions, these nanoheterogeneities (called here lipid nanodomains) can be found in perfect registration (i.e., nanodomains in the inner leaflet are registered with the nanodomains in the outer leaflet). Alternatively, they might be interleaflet independent, antiregistered, or located asymmetrically in one bilayer leaflet only. To distinguish these scenarios from each other appears to be an experimental challenge. In this work, we analyzed the potential of Förster resonance energy transfer to characterize interleaflet organization of nanodomains. We generated in silico time-resolved fluorescence decays for a large set of virtual as well as real donor/acceptor pairs distributed over the bilayer containing registered, independent, antiregistered, or asymmetrically distributed nanodomains. In this way, we were able to identify conditions that gave satisfactory or unsatisfactory resolution. Overall, Förster resonance energy transfer appears as a robust method that, when using donor/acceptor pairs with good characteristics, yields otherwise difficult-to-reach characteristics of membrane lipid nanodomains.

J Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences Prague Czech Republic

J Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences Prague Czech Republic; Department of Physical and Macromolecular Chemistry Faculty of Science Charles University Prague Czech Republic

J Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences Prague Czech Republic; Faculty of Mathematics and Physics Charles University Prague Czech Republic

Zobrazit více v PubMed

Nickels J.D., Smith J.C., Cheng X. Lateral organization, bilayer asymmetry, and inter-leaflet coupling of biological membranes. Chem. Phys. Lipids. 2015;192:87–99. PubMed

Grzybek M., Gutmann T., Coskun Ü. CRC Press; 2014. Cell Membrane Nanodomains.

Goñi F.M., Alonso A., Contreras F.X. eLS. Wiley; 2020. Membrane nanodomains; pp. 1–8.

Bernardino de la Serna J., Schütz G.J., et al. Cebecauer M. There is No simple model of the plasma membrane organization. Front. Cell Dev. Biol. 2016;4:106–117. PubMed PMC

Cebecauer M., Amaro M., et al. Hof M. Membrane lipid nanodomains. Chem. Rev. 2018;118:11259–11297. PubMed

Owen D.M., Magenau A., et al. Gaus K. The lipid raft hypothesis revisited - new insights on raft composition and function from super-resolution fluorescence microscopy. Bioessays. 2012;34:739–747. PubMed

Škerle J., Humpolíčková J., et al. Strisovsky K. Membrane protein dimerization in cell-derived lipid membranes measured by FRET with MC simulations. Biophys. J. 2020;118:1861–1875. PubMed PMC

Koukalová A., Amaro M., et al. Šachl R. Lipid driven nanodomains in giant lipid vesicles are fluid and disordered. Sci. Rep. 2017;7:5460. PubMed PMC

Ashrafzadeh P., Parmryd I. Methods applicable to membrane nanodomain studies? Essays Biochem. 2015;57:57–68. PubMed

Vinklárek I.S., Vel’As L., et al. Šachl R. Experimental evidence of the existence of interleaflet coupled nanodomains: an MC-FRET study. J. Phys. Chem. Lett. 2019;10:2024–2030. PubMed

Sarmento M.J., Hof M., Šachl R. Interleaflet coupling of lipid nanodomains – insights from in vitro systems. Front. Cell Dev. Biol. 2020;8:284. PubMed PMC

Blosser M.C., Honerkamp-Smith A.R., et al. Keller S.L. Transbilayer colocalization of lipid domains explained via measurement of strong coupling parameters. Biophys. J. 2015;109:2317–2327. PubMed PMC

Šachl R., Humpolíčková J., et al. Hof M. Limitations of electronic energy transfer in the determination of lipid nanodomain sizes. Biophys. J. 2011;101:L60–L62. PubMed PMC

King C., Raicu V., Hristova K. Understanding the FRET signatures of interacting membrane proteins. J. Biol. Chem. 2017;292:5291–5310. PubMed PMC

Chmelová B., Humpolíčková J., et al. Šachl R. In: Fluorescence Microscopy and Spectroscopy in Biology. Šachl R., Amaro M., editors. Springer; 2022. The analysis of in-membrane nanoscopic aggregation of lipids and proteins by MC-FRET. in press.

Šachl R., Boldyrev I., Johansson L.B.A. Localisation of BODIPY-labelled phosphatidylcholines in lipid bilayers. Phys. Chem. Chem. Phys. 2010;12:6027–6034. PubMed

Sarmento M.J., Owen M.C., et al. Šachl R. The impact of the glycan headgroup on the nanoscopic segregation of gangliosides. Biophys. J. 2021;120:5530–5543. PubMed PMC

Sarmento M.J., Ricardo J.C., et al. Šachl R. Organization of gangliosides into membrane nanodomains. FEBS Lett. 2020;594:3668–3697. PubMed

Loura L.M., Fedorov A., Prieto M. Partition of membrane probes in a gel/fluid two-component lipid system: a fluorescence resonance energy transfer study. Biochim. Biophys. Acta Biomembr. 2000;1467:101–112. PubMed

Enoki T.A., Heberle F.A., Feigenson G.W. FRET detects the size of nanodomains for coexisting liquid-disordered and liquid-ordered phases. Biophys. J. 2018;114:1921–1935. PubMed PMC

De Almeida R.F.M., Loura L.M.S., et al. Prieto M. Lipid rafts have different sizes depending on membrane composition: a time-resolved fluorescence resonance energy transfer study. J. Mol. Biol. 2005;346:1109–1120. PubMed

Heberle F.A., Wu J., et al. Feigenson G.W. Comparison of three ternary lipid bilayer mixtures: FRET and ESR reveal nanodomains. Biophys. J. 2010;99:3309–3318. PubMed PMC

Štefl M., Šachl R., et al. Hof M. Dynamics and size of cross-linking-induced lipid nanodomains in model membranes. Biophys. J. 2012;102:2104–2113. PubMed PMC

Bordovsky S.S., Wong C.S., et al. Sasaki D.Y. Engineering lipid structure for recognition of the liquid ordered membrane phase. Langmuir. 2016;32:12527–12533. PubMed

Taylor G.J., Heberle F.A., et al. Sarles S.A. Capacitive detection of low-enthalpy, higher-order phase transitions in synthetic and natural composition lipid membranes. Langmuir. 2017;33:10016–10026. PubMed

Okuno D., Iino R., Noji H. Springer Berlin Heidelberg; Berlin, Heidelberg: 2013. Encyclopedia of Biophysics.

Struck D.K., Hoekstra D., Pagano R.E. Use of resonance energy transfer to monitor membrane fusion. Biochemistry. 1981;20:4093–4099. PubMed

Lira R.B., Robinson T., et al. Riske K.A. Highly efficient protein-free membrane fusion: a giant vesicle study. Biophys. J. 2019;116:79–91. PubMed PMC

Franzl T., Koktysh D.S., et al. Gaponik N. Fast energy transfer in layer-by-layer assembled CdTe nanocrystal bilayers. Appl. Phys. Lett. 2004;84:2904–2906.

Doktorova M., Heberle F.A., et al. Marquardt D. Preparation of asymmetric phospholipid vesicles for use as cell membrane models. Nat. Protoc. 2018;13:2086–2101. PubMed PMC

Šachl R., Amaro M., et al. Hof M. On multivalent receptor activity of GM1 in cholesterol containing membranes. Biochim. Biophys. Acta. 2015;1853:850–857. PubMed

Amaro M., Šachl R., et al. Hof M. GM1 ganglioside inhibits b-amyloid oligomerization induced by sphingomyelin. Angew. Chem., Int. Ed. Engl. 2016;55:9411–9415. PubMed PMC

Šachl R., Johansson L.B., Hof M. Förster resonance energy transfer (FRET) between heterogeneously distributed probes: application to lipid nanodomains and pores. Int. J. Mol. Sci. 2012;13:16141–16156. PubMed PMC

Baumann J., Fayer M.D. Excitation transfer in dissordered two-dimensional and anisotropic 3-dimensional systems - effects of spatial geometry on time-resolved observables. J. Chem. Phys. 1986;85:4087–4107.

Which Moiety Drives Gangliosides to Form Nanodomains?