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Low energy cost for optimal speed and control of membrane fusion

Francois-Martin, C; Rothman, JE; Pincet, F; (2017) Low energy cost for optimal speed and control of membrane fusion. Proceedings of the National Academy of Sciences of the United States of America , 114 (6) pp. 1238-1241. 10.1073/pnas.1621309114. Green open access

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Abstract

Membrane fusion is the cell’s delivery process, enabling its many compartments to receive cargo and machinery for cell growth and intercellular communication. The overall activation energy of the process must be large enough to prevent frequent and nonspecific spontaneous fusion events, yet must be low enough to allow it to be overcome upon demand by specific fusion proteins [such as soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs)]. Remarkably, to the best of our knowledge, the activation energy for spontaneous bilayer fusion has never been measured. Multiple models have been developed and refined to estimate the overall activation energy and its component parts, and they span a very broad range from 20 kBT to 150 kBT, depending on the assumptions. In this study, using a bulk lipid-mixing assay at various temperatures, we report that the activation energy of complete membrane fusion is at the lowest range of these theoretical values. Typical lipid vesicles were found to slowly and spontaneously fully fuse with activation energies of ∼30 kBT. Our data demonstrate that the merging of membranes is not nearly as energy consuming as anticipated by many models and is ideally positioned to minimize spontaneous fusion while enabling rapid, SNARE-dependent fusion upon demand.

Type: Article
Title: Low energy cost for optimal speed and control of membrane fusion
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.1621309114
Publisher version: http://doi.org/10.1073/pnas.1621309114
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Membrane fusion, activation energy, liposome, energy landscape
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
URI: https://discovery.ucl.ac.uk/id/eprint/10044923
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