Flutuações de não equilíbrio de membranas lipídicas pela proteína motora rotativa F1F0-ATP sintase

quinta-feira, novembro 23, 2017

Nonequilibrium fluctuations of lipid membranes by the rotating motor protein F1F0-ATP synthase

Víctor G. Almendro-Vedia a,b, Paolo Natale a,b, Michael Mell a, Stephanie Bonneau c, Francisco Monroy a,b, Frederic Joubert c, and Iván López-Montero a,b,1 

Author Affiliations

a Departamento Química Física I, Universidad Complutense de Madrid, 28040 Madrid, Spain;

b Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain;

c Laboratoire Jean Perrin, CNRS, Université Pierre et Marie Curie, 75005 Paris, France

Edited by Olaf S. Andersen, Weill Cornell Medical College, New York, NY, and accepted by Editorial Board Member Ramon Latorre September 7, 2017 (received for review January 23, 2017)


The shape of biological membranes is constantly remodeled and maintained out of equilibrium by active proteins. The functional capacity of membrane deformation is mainly determined by the mechanical interplay between protein activity and bending elasticity. In our experiments, we find that ATP synthase, a rotating membrane protein that synthesizes the biochemical energy in cells through proton-pumping activity across the membrane, promotes localized nonequilibrium membrane fluctuations when reconstituted in giant lipid vesicles. The large membrane deformations emerge from the pumping action of rotating proteins clustered at specific emplacements in the membrane. Our results pave the way to new experimental realizations to explore the collective effects of rotating ATP synthases and their possible biological implications for biomembrane organization and protein functionality.


ATP synthase is a rotating membrane protein that synthesizes ATP through proton-pumping activity across the membrane. To unveil the mechanical impact of this molecular active pump on the bending properties of its lipid environment, we have functionally reconstituted the ATP synthase in giant unilamellar vesicles and tracked the membrane fluctuations by means of flickering spectroscopy. We find that ATP synthase rotates at a frequency of about 20 Hz, promoting large nonequilibrium deformations at discrete hot spots in lipid vesicles and thus inducing an overall membrane softening. The enhanced nonequilibrium fluctuations are compatible with an accumulation of active proteins at highly curved membrane sites through a curvature−protein coupling mechanism that supports the emergence of collective effects of rotating ATP synthases in lipid membranes.

giant vesicles active membranes mechanical properties flickering spectroscopy biological nanorotors


1To whom correspondence should be addressed. Email: ivanlopez@quim.ucm.es.

Author contributions: I.L.-M. designed research; V.G.A.-V. and P.N. performed research; M.M. and F.M. contributed new reagents/analytic tools; V.G.A.-V., S.B., F.M., F.J., and I.L.-M. analyzed data; and P.N., S.B., F.M., F.J., and I.L.-M. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission. O.S.A. is a guest editor invited by the Editorial Board.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1701207114/-/DCSupplemental.

Copyright © 2017 the Author(s). Published by PNAS.

This is an open access article distributed under the PNAS license.