title: Low energy cost for optimal speed and control of membrane fusion.
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.
authors.affiliation: Laboratoire de Physique Statistique, Ecole Normale Supérieure, Paris Sciences et Lettres Research University, 75005 Paris, France.|Laboratoire de Physique Statistique, Université Paris Diderot Sorbonne Paris Cité, 75005 Paris, France.|Laboratoire de Physique Statistique, Sorbonne Universités, Université Pierre et Marie Curie, Univ Paris 06, CNRS, 75005 Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: François-Martin
authors.affiliation: Department of Cell Biology, School of Medicine, Yale University, New Haven, CT 06520; pincet@lps.ens.fr james.rothman@yale.edu.|Nanobiology Institute, School of Medicine, Yale University, New Haven, CT 06520.
authors.forename: James E
authors.initials: JE
authors.lastname: Rothman
authors.affiliation: Laboratoire de Physique Statistique, Ecole Normale Supérieure, Paris Sciences et Lettres Research University, 75005 Paris, France; pincet@lps.ens.fr james.rothman@yale.edu.|Laboratoire de Physique Statistique, Université Paris Diderot Sorbonne Paris Cité, 75005 Paris, France.|Laboratoire de Physique Statistique, Sorbonne Universités, Université Pierre et Marie Curie, Univ Paris 06, CNRS, 75005 Paris, France.|Department of Cell Biology, School of Medicine, Yale University, New Haven, CT 06520.|Nanobiology Institute, School of Medicine, Yale University, New Haven, CT 06520.
authors.forename: Frederic
authors.initials: F
authors.lastname: Pincet
mesh_terms: D008561:Membrane Fusion; D008563:Membrane Lipids / Q000737:chemistry*; D008854:Microscopy, Electron; D008954:Models, Biological; D013696:Temperature
chemical_list: D008563:Membrane Lipids
keywords: activation energy; energy landscape; lipid-mixing assay; liposome; membrane fusion