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  The glycolipid GM1 reshapes asymmetric biomembranes and giant vesicles by curvature generation

Dasgupta, R., Miettinen, M. S., Fricke, N., Lipowsky, R., & Dimova, R. (2018). The glycolipid GM1 reshapes asymmetric biomembranes and giant vesicles by curvature generation. Proceedings of the National Academy of Sciences of the United States of America, 115(22), 5756-5761. doi:10.1073/pnas.1722320115.

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Dasgupta, Raktim1, Author           
Miettinen, Markus S.2, Author           
Fricke, Nico1, Author           
Lipowsky, Reinhard3, Author                 
Dimova, Rumiana1, Author                 
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1Rumiana Dimova, Theorie & Bio-Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863328              
2Theorie & Bio-Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863289              
3Reinhard Lipowsky, Theorie & Bio-Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863327              

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 Abstract: The multifaceted involvement of GM1 as a ligand in many cellular functions has been well recognized. We find that GM1 readily desorbs from the membrane of cell-sized model biomimetic systems (giant unilamellar vesicles). The desorption is unbalanced, creating an asymmetry between the bilayer leaflets. This results in reshaping weakly curved membranes into nanotubular invaginations stabilized by the membrane spontaneous curvature, which we quantify experimentally. Computer simulations confirm the experimental results. Uncovering the role of GM1 as a fine regulator of membrane curvature broadens our perspective on its important function in reshaping neuronal membranes and emphasizes that GM1 desorption can strongly affect the cell membrane morphology.The ganglioside GM1 is present in neuronal membranes at elevated concentrations with an asymmetric spatial distribution. It is known to generate curvature and can be expected to strongly influence the neuron morphology. To elucidate these effects, we prepared giant vesicles with GM1 predominantly present in one leaflet of the membrane, mimicking the asymmetric GM1 distribution in neuronal membranes. Based on pulling inward and outward tubes, we developed a technique that allowed the direct measurement of the membrane spontaneous curvature. Using vesicle electroporation and fluorescence intensity analysis, we were able to quantify the GM1 asymmetry across the membrane and to subsequently estimate the local curvature generated by the molecule in the bilayer. Molecular-dynamics simulations confirm the experimentally determined dependence of the membrane spontaneous curvature as a function of GM1 asymmetry. GM1 plays a crucial role in connection with receptor proteins. Our results on curvature generation of GM1 point to an additional important role of this ganglioside, namely in shaping neuronal membranes.

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Language(s): eng - English
 Dates: 2018-052018
 Publication Status: Issued
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 Identifiers: DOI: 10.1073/pnas.1722320115
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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proceedings of the National Academy of Sciences of the USA
  Other : Proc. Acad. Sci. USA
  Other : Proc. Acad. Sci. U.S.A.
  Abbreviation : PNAS
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 115 (22) Sequence Number: - Start / End Page: 5756 - 5761 Identifier: ISSN: 0027-8424