Membrane bending by protein-protein crowding

Jeanne C. Stachowiak, Eva M. Schmid, Christopher J. Ryan, Hyoung Sook Ann, Darryl Y. Sasaki, Michael Sherman, Phillip L. Geissler, Daniel A. Fletcher, Carl C. Hayden

Research output: Contribution to journalArticle

241 Citations (Scopus)

Abstract

Curved membranes are an essential feature of dynamic cellular structures, including endocytic pits, filopodia protrusions and most organelles. It has been proposed that specialized proteins induce curvature by binding to membranes through two primary mechanisms: membrane scaffolding by curved proteins or complexes; and insertion of wedge-like amphipathic helices into the membrane. Recent computational studies have raised questions about the efficiency of the helix-insertion mechanism, predicting that proteins must cover nearly 100% of the membrane surface to generate high curvature, an improbable physiological situation. Thus, at present, we lack a sufficient physical explanation of how protein attachment bends membranes efficiently. On the basis of studies of epsin1 and AP180, proteins involved in clathrin-mediated endocytosis, we propose a third general mechanism for bending fluid cellular membranes: protein-protein crowding. By correlating membrane tubulation with measurements of protein densities on membrane surfaces, we demonstrate that lateral pressure generated by collisions between bound proteins drives bending. Whether proteins attach by inserting a helix or by binding lipid heads with an engineered tag, protein coverage above ∼20% is sufficient to bend membranes. Consistent with this crowding mechanism, we find that even proteins unrelated to membrane curvature, such as green fluorescent protein (GFP), can bend membranes when sufficiently concentrated. These findings demonstrate a highly efficient mechanism by which the crowded protein environment on the surface of cellular membranes can contribute to membrane shape change.

Original languageEnglish (US)
Pages (from-to)944-949
Number of pages6
JournalNature Cell Biology
Volume14
Issue number9
DOIs
StatePublished - Sep 2012

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Membrane Proteins
Membranes
Proteins
Clathrin
Pseudopodia
Cellular Structures
Endocytosis
Green Fluorescent Proteins
Organelles
Lipids
Pressure

ASJC Scopus subject areas

  • Cell Biology

Cite this

Stachowiak, J. C., Schmid, E. M., Ryan, C. J., Ann, H. S., Sasaki, D. Y., Sherman, M., ... Hayden, C. C. (2012). Membrane bending by protein-protein crowding. Nature Cell Biology, 14(9), 944-949. https://doi.org/10.1038/ncb2561

Membrane bending by protein-protein crowding. / Stachowiak, Jeanne C.; Schmid, Eva M.; Ryan, Christopher J.; Ann, Hyoung Sook; Sasaki, Darryl Y.; Sherman, Michael; Geissler, Phillip L.; Fletcher, Daniel A.; Hayden, Carl C.

In: Nature Cell Biology, Vol. 14, No. 9, 09.2012, p. 944-949.

Research output: Contribution to journalArticle

Stachowiak, JC, Schmid, EM, Ryan, CJ, Ann, HS, Sasaki, DY, Sherman, M, Geissler, PL, Fletcher, DA & Hayden, CC 2012, 'Membrane bending by protein-protein crowding', Nature Cell Biology, vol. 14, no. 9, pp. 944-949. https://doi.org/10.1038/ncb2561
Stachowiak JC, Schmid EM, Ryan CJ, Ann HS, Sasaki DY, Sherman M et al. Membrane bending by protein-protein crowding. Nature Cell Biology. 2012 Sep;14(9):944-949. https://doi.org/10.1038/ncb2561
Stachowiak, Jeanne C. ; Schmid, Eva M. ; Ryan, Christopher J. ; Ann, Hyoung Sook ; Sasaki, Darryl Y. ; Sherman, Michael ; Geissler, Phillip L. ; Fletcher, Daniel A. ; Hayden, Carl C. / Membrane bending by protein-protein crowding. In: Nature Cell Biology. 2012 ; Vol. 14, No. 9. pp. 944-949.
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