Protein-Lipid Interplay in Fusion and Fission of Biological Membranes

Chernomordik, Leonid V.; Kozlov, Michael M.

doi:10.1146/annurev.biochem.72.121801.161504

Cited by 710 publications

(816 citation statements)

References 184 publications

(259 reference statements)

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“…Chernomordik et al 17 . However, comparing the obtained I-V characteristics of a monoolein-HD with the I-V characteristics of a monolein bilayer reported for a similar geometry 14 we find characteristic differences in their stability.…”

Section: Realization and Characterization Of A Membrane Fusion Eventmentioning

confidence: 99%

Fast membrane hemifusion via dewetting between lipid bilayers

2014

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The behavior of lipid bilayer is important to understand the functionality of cells like the trafficking of ions between cells. Standard procedures to explore the properties of lipid bilayer and hemifused states typically use either supported membranes or vesicles. Both techniques have several shortcoming in terms of bio relevance or accessibility for measurements. In this article the formation of individual free standing hemifused states between model cell membranes is studied using an optimized microfluidic scheme wh ich allows for simultaneous optical and electrophysiological measurements. In a first step, two model membranes are formed at a desired location within a microfluidic device using a variation of the droplet interface bilayer (DiB) technique. In a second st ep, the two model membranes are brought into contact forming a single hemifused state. For all tested lipids, the hemifused state between free standing membranes form within hundreds of milliseconds, i.e. several orders of magnitude faster than reported in literature. The formation of a hemifused state is observed as a two stage process, whereas the second stage can be explained as a dewetting process in no-slip boundary condition. The formed hemifusion states are long living and a single fusion event can be observed when triggered by an applied electric field as demonstrated for monoolein.

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Section: Realization and Characterization Of A Membrane Fusion Eventmentioning

confidence: 99%

Fast membrane hemifusion via dewetting between lipid bilayers

2014

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“…Lipid bilayer bending and tilt of hydrocarbon chains can provide sufficient lateral tension to drive pore opening in a nonbilayer intermediate (Chernomordik and Kozlov, 2003). This implies that membrane permeabilization is not necessarily mediated by a proteinaceous pore, but rather results from the concerted actions of proteins and particular lipids.…”

Section: Importance Of Lipids and Membrane Topologymentioning

confidence: 99%

“…Membrane fusion and fission engage rupture and deformation of lipid bilayers, and involve destabilized monolayer intermediates (Chernomordik and Kozlov, 2003). The two membranes are first brought in close contact, then some hydrophobic monolayer discontinuity appears that enables the rupture of the bilayer and the formation of a fusion stalk intermediate.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria and cancer: is there a morphological connection?

2006

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Mitochondria are key players in several cellular functions including growth, division, energy metabolism, and apoptosis. The mitochondrial network undergoes constant remodelling and these morphological changes are of direct relevance for the role of this organelle in cell physiology. Mitochondrial dysfunction contributes to a number of human disorders and may aid cancer progression. Here, we summarize the recent contributions made in the field of mitochondrial dynamics and discuss their impact on our understanding of cell function and tumorigenesis.

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“…The membrane merging is catalyzed by diverse fusion machineries comprising several proteins such as SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) or viral fusion proteins. The fusion processes share common features on the membrane level: two opposing membranes specifically approach closely and merge via a stalk intermediate and a fusion pore is opened (1). The natural fusion machineries are thought to stabilize the intermediate states of lipid rearrangement and/or aid in overcoming the energetic barriers between them, employing concerted protein-protein and protein-membrane interactions (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

A Coiled-Coil Peptide Shaping Lipid Bilayers upon Fusion

Rabe

Aisenbrey

Pluháčková

et al. 2016

Biophysical Journal

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A system based on two designed peptides, namely the cationic peptide K, (KIAALKE) 3 , and its complementary anionic counterpart called peptide E, (EIAALEK) 3 , has been used as a minimal model for membrane fusion, inspired by SNARE proteins. Although the fact that docking of separate vesicle populations via the formation of a dimeric E/K coiled-coil complex can be rationalized, the reasons for the peptides promoting fusion of vesicles cannot be fully explained. Therefore it is of significant interest to determine how the peptides aid in overcoming energetic barriers during lipid rearrangements leading to fusion. In this study, investigations of the peptides' interactions with neutral PC/PE/cholesterol membranes by fluorescence spectroscopy show that tryptophan-labeled K* binds to the membrane (K K*~6 .2 10 3 M À1 ), whereas E* remains fully water-solvated. 15 N-NMR spectroscopy, depth-dependent fluorescence quenching, CD-spectroscopy experiments, and MD simulations indicate a helix orientation of K* parallel to the membrane surface. Solid-state 31 P-NMR of oriented lipid membranes was used to study the impact of peptide incorporation on lipid headgroup alignment. The membrane-immersed K* is found to locally alter the bilayer curvature, accompanied by a change of headgroup orientation relative to the membrane normal and of the lipid composition in the vicinity of the bound peptide. The NMR results were supported by molecular dynamics simulations, which showed that K reorganizes the membrane composition in its vicinity, induces positive membrane curvature, and enhances the lipid tail protrusion probability. These effects are known to be fusion relevant. The combined results support the hypothesis for a twofold role of K in the mechanism of membrane fusion: 1) to bring opposing membranes into close proximity via coiled-coil formation and 2) to destabilize both membranes thereby promoting fusion.

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Protein-Lipid Interplay in Fusion and Fission of Biological Membranes

Cited by 710 publications

References 184 publications

Fast membrane hemifusion via dewetting between lipid bilayers

Fast membrane hemifusion via dewetting between lipid bilayers

Mitochondria and cancer: is there a morphological connection?

A Coiled-Coil Peptide Shaping Lipid Bilayers upon Fusion

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