Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year

IMPACT FACTOR 2017: 3.022

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 1.562
Source Normalized Impact per Paper (SNIP) 2017: 0.705

See all formats and pricing
More options …
Volume 395, Issue 3


Reshaping biological membranes in endocytosis: crossing the configurational space of membrane-protein interactions

Mijo Simunovic
  • Institut Curie, Centre National de la Recherche Scientifique Unité Mixte de Recherche 168, Université Pierre et Marie Curie, F-75248 Paris, France
  • Department of Physics, Université Paris Diderot, 10, rue Alice Domon et Léonie Duquet, 75013 Paris, France
  • Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Patricia Bassereau
  • Corresponding author
  • Institut Curie, Centre National de la Recherche Scientifique Unité Mixte de Recherche 168, Université Pierre et Marie Curie, F-75248 Paris, France
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-12-17 | DOI: https://doi.org/10.1515/hsz-2013-0242


Lipid membranes are highly dynamic. Over several decades, physicists and biologists have uncovered a number of ways they can change the shape of membranes or alter their phase behavior. In cells, the intricate action of membrane proteins drives these processes. Considering the highly complex ways proteins interact with biological membranes, molecular mechanisms of membrane remodeling still remain unclear. When studying membrane remodeling phenomena, researchers often observe different results, leading them to disparate conclusions on the physiological course of such processes. Here we discuss how combining research methodologies and various experimental conditions contributes to the understanding of the entire phase space of membrane-protein interactions. Using the example of clathrin-mediated endocytosis we try to distinguish the question ‘how can proteins remodel the membrane?’ from ‘how do proteins remodel the membrane in the cell?’ In particular, we consider how altering physical parameters may affect the way membrane is remodeled. Uncovering the full range of physical conditions under which membrane phenomena take place is key in understanding the way cells take advantage of membrane properties in carrying out their vital tasks.

Keywords: BAR domain; clathrin; membrane remodeling; membrane tension; multiscale simulation


  • Alberts, B. (2002). Molecular biology of the cell, 4th edition. (New York, USA: Garland Science).Google Scholar

  • Ayton, G.S. and Voth, G.A. (2010). Multiscale simulation of protein mediated membrane remodeling. Semin. Cell Dev. Biol. 21, 357–362.PubMedCrossrefGoogle Scholar

  • Bai, J., Hu, Z., Dittman, J.S., Pym, E.C., and Kaplan, J.M. (2010). Endophilin functions as a membrane-bending molecule and is delivered to endocytic zones by exocytosis. Cell 143, 430–441.Google Scholar

  • Baumgart, T., Hess, S.T., and Webb, W.W. (2003). Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension. Nature 425, 821–824.Google Scholar

  • Bhatia, V.K., Hatzakis, N.S., and Stamou, D. (2010). A unifying mechanism accounts for sensing of membrane curvature by BAR domains, amphipathic helices and membrane-anchored proteins. Semin. Cell Dev. Biol. 21, 381–390.PubMedCrossrefGoogle Scholar

  • Bhatia, V.K., Madsen, K.L., Bolinger, P.Y., Kunding, A., Hedegard, P., Gether, U., and Stamou, D. (2009). Amphipathic motifs in BAR domains are essential for membrane curvature sensing. EMBO J. 28, 3303–3314.CrossrefPubMedGoogle Scholar

  • Bickel, T., Jeppesen, C., and Marques, C.M. (2001). Local entropic effects of polymers grafted to soft interfaces. Eur. Phys. J. E. 4, 33–43.CrossrefGoogle Scholar

  • Blood, P.D. and Voth, G.A. (2006). Direct observation of Bin/amphiphysin/Rvs (BAR). domain-induced membrane curvature by means of molecular dynamics simulations. Proc. Natl. Acad. Sci. USA 103, 15068–15072.Google Scholar

  • Boucrot, E., Pick, A., Camdere, G., Liska, N., Evergren, E., McMahon, H.T., and Kozlov, M.M. (2012). Membrane fission is promoted by insertion of amphipathic helices and is restricted by crescent BAR domains. Cell 149, 124–136.Google Scholar

  • Boulant, S., Kural, C., Zeeh, J.C., Ubelmann, F., and Kirchhausen, T. (2011). Actin dynamics counteract membrane tension during clathrin-mediated endocytosis. Nat. Cell Biol. 13, 1124–1131.PubMedCrossrefGoogle Scholar

  • Breidenich, M., Netz, R.R., and Lipowsky, R. (2000). The shape of polymer-decorated membranes. Europhys. Lett. 49, 431–437.CrossrefGoogle Scholar

  • Campelo, F., McMahon, H.T., and Kozlov, M.M. (2008). The hydrophobic insertion mechanism of membrane curvature generation by proteins. Biophys. J. 95, 2325–2339.PubMedCrossrefGoogle Scholar

  • Cocucci, E., Aguet, F., Boulant, S., and Kirchhausen, T. (2012). The first five seconds in the life of a clathrin-coated pit. Cell 150, 495–507.Google Scholar

  • Cullis, P.R. and de Kruijff, B. (1979). Lipid polymorphism and the functional roles of lipids in biological membranes. Biochim. Biophys. Acta 559, 399–420.Google Scholar

  • Dai, J.W. and Sheetz, M.P. (1999). Membrane tether formation from blebbing cells. Biophys. J. 77, 3363–3370.CrossrefPubMedGoogle Scholar

  • Dannhauser, P.N. and Ungewickell, E.J. (2012). Reconstitution of clathrin-coated bud and vesicle formation with minimal components. Nat. Cell Biol. 14, 634–639.CrossrefPubMedGoogle Scholar

  • Doyon, J.B., Zeitler, B., Cheng, J., Cheng, A.T., Cherone, J.M., Santiago, Y., Lee, A.H., Vo, T.D., Doyon, Y., Miller, J.C., et al. (2011). Rapid and efficient clathrin-mediated endocytosis revealed in genome-edited mammalian cells. Nat. Cell Biol. 13, 331–337.PubMedCrossrefGoogle Scholar

  • Drin, G. and Antonny, B. (2010). Amphipathic helices and membrane curvature. FEBS Lett 584, 1840–1847.Google Scholar

  • Farsad, K. and De Camilli, P. (2003). Mechanisms of membrane deformation. Curr. Opin. Cell Biol. 15, 372–381.CrossrefGoogle Scholar

  • Fotin, A., Cheng, Y., Sliz, P., Grigorieff, N., Harrison, S.C., Kirchhausen, T., and Walz, T. (2004). Molecular model for a complete clathrin lattice from electron cryomicroscopy. Nature 432, 573–579.Google Scholar

  • Frost, A., Perera, R., Roux, A., Spasov, K., Destaing, O., Egelman, E.H., De Camilli, P., and Unger, V.M. (2008). Structural basis of membrane invagination by F-BAR domains. Cell 132, 807–817.Google Scholar

  • Goetz, R., Gompper, G., and Lipowsky, R. (1999). Mobility and elasticity of self-assembled membranes. Phys. Rev. Lett. 82, 221–224.CrossrefGoogle Scholar

  • Heinrich, M.C., Capraro, B.R., Tian, A., Isas, J.M., Langen, R., and Baumgart, T. (2010). Quantifying membrane curvature generation of amphiphysin N-BAR domains. J. Phys. Chem. Lett. 1, 3401–3406.CrossrefGoogle Scholar

  • Helfrich, W. (1973). Elastic properties of lipid bilayers: theory and possible experiments. Z. Naturforsch. C 28, 693–703.Google Scholar

  • Helfrich, W. (1989). Hats and saddles in lipid-membranes. Liquid Crystals 5, 1647–1658.CrossrefGoogle Scholar

  • Julicher, F. and Lipowsky, R. (1993). Domain-induced budding of vesicles. Phys. Rev. Lett. 70, 2964–2967.CrossrefPubMedGoogle Scholar

  • Kirchhausen, T. (2009). Imaging endocytic clathrin structures in living cells. Trends Cell Biol. 19, 596–605.PubMedCrossrefGoogle Scholar

  • Kukulski, W., Schorb, M., Kaksonen, M., and Briggs, J.A. (2012). Plasma membrane reshaping during endocytosis is revealed by time-resolved electron tomography. Cell 150, 508–520.Google Scholar

  • Kukulski, W., Schorb, M., Welsch, S., Picco, A., Kaksonen, M., and Briggs, J.A. (2011). Correlated fluorescence and 3D electron microscopy with high sensitivity and spatial precision. J. Cell Biol. 192, 111–119.Google Scholar

  • Lieber, A.D., Yehudai-Resheff, S., Barnhart, E.L., Theriot, J.A., and Keren, K. (2013). membrane tension in rapidly moving cells is determined by cytoskeletal forces. Curr. Biol., 23, 1409–1417.PubMedCrossrefGoogle Scholar

  • Lipowsky, R. (1991). The conformation of membranes. Nature 349, 475–481.Google Scholar

  • Lipowsky, R. (2013). Spontaneous tubulation of membranes and vesicles reveals membrane tension generated by spontaneous curvature. Farad. Discuss. 161, 305–331.Google Scholar

  • Lipowsky, R. and Dimova, R. (2003). Domains in membranes and vesicles. J. Phys. Condens. Matter. 15, S31–S45.CrossrefGoogle Scholar

  • Lipowsky, R. and Sackmann, E. (ed). (1995). Structure and Dynamics of Membranes: From Cells to Vesicles. Elsevier: North Holland, Amsterdam.Google Scholar

  • McMahon, H.T. and Gallop, J.L. (2005). Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438, 590–596.Google Scholar

  • Meinecke, M., Boucrot, E., Camdere, G., Hon, W.C., Mittal, R., and McMahon, H.T. (2013). Cooperative Recruitment of Dynamin and BIN/Amphiphysin/Rvs (BAR). Domain-containing Proteins Leads to GTP-dependent Membrane Scission. J. Biol. Chem. 288, 6651–6661.Google Scholar

  • Mim, C., Cui, H., Gawronski-Salerno, J.A., Frost, A., Lyman, E., Voth, G.A., and Unger, V.M. (2012a). Structural basis of membrane bending by the N-BAR protein endophilin. Cell 149, 137–145.Google Scholar

  • Mim, C., Cui, H.S., Gawronski-Salerno, J.A., Frost, A., Lyman, E., Voth, G.A., and Unger, V.M. (2012b). Structural basis of membrane bending by the N-BAR protein endophilin. Cell 149, 137–145.Google Scholar

  • Mim, C. and Unger, V.M. (2012). Membrane curvature and its generation by BAR proteins. Trends Biochem. Sci. 37, 526–533.PubMedCrossrefGoogle Scholar

  • Morlot, S., Galli, V., Klein, M., Chiaruttini, N., Manzi, J., Humbert, F., Dinis, L., Lenz, M., Cappello, G., and Roux, A. (2012). Membrane shape at the edge of the dynamin helix sets location and duration of the fission reaction. Cell 151, 619–629.Google Scholar

  • Peter, B.J., Kent, H.M., Mills, I.G., Vallis, Y., Butler, P.J., Evans, P.R., and McMahon, H.T. (2004). BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 303, 495–499.Google Scholar

  • Posor, Y., Eichhorn-Gruenig, M., Puchkov, D., Schoneberg, J., Ullrich, A., Lampe, A., Muller, R., Zarbakhsh, S., Gulluni, F., Hirsch, E., et al. (2013). Spatiotemporal control of endocytosis by phosphatidylinositol-3,4-bisphosphate. Nature 499, 233–237.Google Scholar

  • Qualmann, B., Koch, D., and Kessels, M.M. (2011). Let’s go bananas: revisiting the endocytic BAR code. EMBO J. 30, 3501–3515.CrossrefGoogle Scholar

  • Ramakrishnan, N., Kumar, P.B.S., and Ipsen, J.H. (2013). Membrane-mediated aggregation of curvature-inducing nematogens and membrane tubulation. Biophys. J. 104, 1018–1028.PubMedCrossrefGoogle Scholar

  • Ramesh, P., Baroji, Y.F., Reihani, S.N., Stamou, D., Oddershede, L.B., and Bendix, P.M. (2013). FBAR syndapin 1 recognizes and stabilizes highly curved tubular membranes in a concentration dependent manner. Sci. Rep. 3, 1565.Google Scholar

  • Raucher, D. and Sheetz, M.P. (1999). Characteristics of a membrane reservoir buffering membrane tension. Biophys. J. 77, 1992–2002.CrossrefPubMedGoogle Scholar

  • Reynwar, B.J., Illya, G., Harmandaris, V.A., Muller, M.M., Kremer, K., and Deserno, M. (2007). Aggregation and vesiculation of membrane proteins by curvature-mediated interactions. Nature 447, 461–464.Google Scholar

  • Saheki, Y. and De Camilli, P. (2012). Synaptic vesicle endocytosis. Cold Spring Harb. Perspect. Biol. 4, a005645.Google Scholar

  • Saric, A. and Cacciuto, A. (2012). Fluid membranes can drive linear aggregation of adsorbed spherical nanoparticles. Phys. Rev. Lett. 108, 118101.CrossrefPubMedGoogle Scholar

  • Seifert, U. (1997). Configurations of fluid membranes and vesicles. Adv. Phys. 46, 13–137.CrossrefGoogle Scholar

  • Sens, P., Johannes, L., and Bassereau, P. (2008). Biophysical approaches to protein-induced membrane deformations in trafficking. Curr. Opin. Cell Biol. 20, 476–482.CrossrefPubMedGoogle Scholar

  • Simunovic, M., Mim, C., Marlovits, T.C., Resch, G., Unger, V.M., and Voth, G.A. (2013a). Protein-mediated transformation of lipid vesicles into tubular networks. Biophys J. 105, 711–719.CrossrefGoogle Scholar

  • Simunovic, M., Srivastava, A., and Voth, G.A. (2013b). Linear aggregation of proteins on the membrane as a prelude to membrane remodeling. Proc. Natl. Acad. Sci. USA, 110, 20396–20401.CrossrefGoogle Scholar

  • Singh, P., Mahata, P., Baumgart, T., and Das, S.L. (2012). Curvature sorting of proteins on a cylindrical lipid membrane tether connected to a reservoir. Phys. Rev. E, 85.Google Scholar

  • Sorre, B., Callan-Jones, A., Manneville, J.B., Nassoy, P., Joanny, J.F., Prost, J., Goud, B., and Bassereau, P. (2009). Curvature-driven lipid sorting needs proximity to a demixing point and is aided by proteins. Proc. Natl. Acad. Sci. USA 106, 5622–5626.Google Scholar

  • Sorre, B., Callan-Jones, A., Manzi, J., Goud, B., Prost, J., Bassereau, P., and Roux, A. (2012). Nature of curvature coupling of amphiphysin with membranes depends on its bound density. Proc. Natl. Acad. Sci. USA 109, 173–178.Google Scholar

  • Stachowiak, J.C., Schmid, E.M., Ryan, C.J., Ann, H.S., Sasaki, D.Y., Sherman, M.B., Geissler, P.L., Fletcher, D.A., and Hayden, C.C. (2012). Membrane bending by protein-protein crowding. Nat. Cell Biol. 14, 944–949.PubMedCrossrefGoogle Scholar

  • Taylor, M.J., Perrais, D., and Merrifield, C.J. (2011). A High precision survey of the molecular dynamics of mammalian clathrin-mediated endocytosis. Plos Biology, 9, e1000604.CrossrefGoogle Scholar

  • van Weering, J.R.T., Sessions, R.B., Traer, C.J., Kloer, D.P., Bhatia, V.K., Stamou, D., Carlsson, S.R., Hurley, J.H., and Cullen, P.J. (2012). Molecular basis for SNX-BAR-mediated assembly of distinct endosomal sorting tubules. EMBO J. 31, 4466–4480.CrossrefGoogle Scholar

  • Verstreken, P., Kjaerulff, O., Lloyd, T.E., Atkinson, R., Zhou, Y., Meinertzhagen, I.A., and Bellen, H.J. (2002). Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release. Cell 109, 101–112.Google Scholar

  • Weinberg, J. and Drubin, D.G. (2012). Clathrin-mediated endocytosis in budding yeast. Trends Cell Biol, 22, 1–13.CrossrefPubMedGoogle Scholar

  • Yin, Y., Arkhipov, A., and Schulten, K. (2009). Simulations of Membrane Tubulation by Lattices of Amphiphysin N-BAR Domains. Structure 17, 882–892.Google Scholar

  • Zhu, C., Das, S.L., and Baumgart, T. (2012). Nonlinear sorting, curvature generation, and crowding of endophilin N-BAR on tubular membranes. Biophys. J. 102, 1837–1845.CrossrefGoogle Scholar

About the article

Mijo Simunovic

Mijo Simunovic is a PhD student in chemistry at the University of Chicago and in physics at the Curie Institute in Paris. In his research, he combines coarse-grained theoretical techniques in the Voth group with experimental biophysical methods at the Bassereau group to study the physics underlying protein-induced membrane remodeling phenomena. Before joining these two groups, he received his BS and MS in physical chemistry from the University of Zagreb, where he employed theoretical and experimental approaches in investigating problems in synthetic and quantum chemistry.

Patricia Bassereau

Patricia Bassereau is currently Directrice de Recherche, CNRS at the Curie Institute in Paris. After spending 7 years in Montpellier (GDPC) working on the structure of surfactant-based phases, and a year as a visiting scientist at the Almaden IBM Center (San Jose, USA) on the structure of thin polymer films, she moved in 1993 to the Curie Institute. She initially investigated the interactions of soluble proteins with polymer monolayers. In the last 15 years, she has been working in the field of ‘physics for cell biology’. She has developed a multidisciplinary approach to understand the role of lipid membranes in important cellular functions such as intracellular trafficking, endo/exocytosis, transmembrane ion transport (‘active membranes’), or cell adhesion.

Corresponding author: Patricia Bassereau, Institut Curie, Centre National de la Recherche Scientifique Unité Mixte de Recherche 168, Université Pierre et Marie Curie, F-75248 Paris, France, e-mail:

Received: 2013-08-20

Accepted: 2013-12-16

Published Online: 2013-12-17

Published in Print: 2014-03-01

Citation Information: Biological Chemistry, Volume 395, Issue 3, Pages 275–283, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2013-0242.

Export Citation

©2014 by Walter de Gruyter Berlin Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Oleg Milberg, Akiko Shitara, Seham Ebrahim, Andrius Masedunskas, Muhibullah Tora, Duy T. Tran, Yun Chen, Mary Anne Conti, Robert S. Adelstein, Kelly G. Ten Hagen, and Roberto Weigert
The Journal of Cell Biology, 2017, Volume 216, Number 7, Page 1925
Daryna Tarasenko, Mariam Barbot, Daniel C. Jans, Benjamin Kroppen, Boguslawa Sadowski, Gudrun Heim, Wiebke Möbius, Stefan Jakobs, and Michael Meinecke
The Journal of Cell Biology, 2017, Volume 216, Number 4, Page 889
Mijo Simunovic, Gregory A. Voth, Andrew Callan-Jones, and Patricia Bassereau
Trends in Cell Biology, 2015, Volume 25, Number 12, Page 780
Sónia Troeira Henriques, Yen-Hua Huang, Stephanie Chaousis, Marc-Antoine Sani, Aaron G. Poth, Frances Separovic, and David J. Craik
Chemistry & Biology, 2015, Volume 22, Number 8, Page 1087
Mijo Simunovic, Ka Yee C. Lee, and Patricia Bassereau
Soft Matter, 2015, Volume 11, Number 25, Page 5030

Comments (0)

Please log in or register to comment.
Log in