Metabolic Precursor of Cholesterol Causes Formation of Chained Aggregates of Liquid-Ordered Domains

Staneva, Galya; Osipenko, Denis S.; Galimzyanov, Timur R.; Павлов, Константин; Akimov, Sergey A.

doi:10.1021/acs.langmuir.5b03990

Cited by 32 publications

(39 citation statements)

References 57 publications

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“…The deformation is treated according the Hamm–Kozlov model [ 53 ], which has proven itself in the description of membrane processes [ 43 , 59 , 61 , 62 ]. A field of unit director vectors n characterizing the average orientation of lipid molecules is introduced for description of the membrane monolayer deformations.…”

Section: Methodsmentioning

confidence: 99%

Switching between Successful and Dead-End Intermediates in Membrane Fusion

Molotkovsky

Galimzyanov

Jiménez-Munguía

et al. 2017

IJMS

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Fusion of cellular membranes during normal biological processes, including proliferation, or synaptic transmission, is mediated and controlled by sophisticated protein machinery ensuring the preservation of the vital barrier function of the membrane throughout the process. Fusion of virus particles with host cell membranes is more sparingly arranged and often mediated by a single fusion protein, and the virus can afford to be less discriminative towards the possible different outcomes of fusion attempts. Formation of leaky intermediates was recently observed in some fusion processes, and an alternative trajectory of the process involving formation of π-shaped structures was suggested. In this study, we apply the methods of elasticity theory and Lagrangian formalism augmented by phenomenological and molecular geometry constraints and boundary conditions to investigate the traits of this trajectory and the drivers behind the choice of one of the possible scenarios depending on the properties of the system. The alternative pathway proved to be a dead end, and, depending on the parameters of the participating membranes and fusion proteins, the system can either reversibly enter the corresponding “leaky” configuration or be trapped in it. A parametric study in the biologically relevant range of variables emphasized the fusion protein properties crucial for the choice of the fusion scenario.

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Section: Methodsmentioning

confidence: 99%

Switching between Successful and Dead-End Intermediates in Membrane Fusion

Molotkovsky

Galimzyanov

Jiménez-Munguía

et al. 2017

IJMS

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“…For the unidimensional approach to be valid, the domain size should be much larger than the characteristic decay length of membrane deformations, λ. As λ ~ 1-2 nm 20,39,41 , the assumption of the straight boundary is valid for domains larger than about 10 nm in radius, i.e. almost for any observable domain 42 .…”

Section: Statement Of the Problemmentioning

confidence: 99%

“…The energy of the contact might be decreased at the expense of membrane deformations in the vicinity of the boundary, leading to the reduction, down to zero, of the step amplitude 36 . The elastic energy stored in membrane deformations is minimal when the L o domains in opposing monolayers are not exactly in register, but their boundaries are laterally shifted by 2-4 nm with respect to each other 20,[37][38][39] . Thus, the contact of two bilayer L o and L d phases occurs across the intermediate region of 2-4 nm width, where one monolayer is in the L o state and the other monolayer is in the L d state.…”

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confidence: 99%

Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting

Pinigin

Kondrashov

Jiménez-Munguía

et al. 2020

Sci Rep

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Liquid-ordered lipid domains represent a lateral inhomogeneity in cellular membranes. these domains have elastic and physicochemical properties different from those of the surrounding membrane. in particular, their thickness exceeds that of the disordered membrane. thus, elastic deformations arise at the domain boundary in order to compensate for the thickness mismatch. in equilibrium, the deformations lead to an incomplete register of monolayer ordered domains: the elastic energy is minimal if domains in opposing monolayers lie on the top of each other, and their boundaries are laterally shifted by about 3 nm. This configuration introduces a region, composed of one ordered and one disordered monolayers, with an intermediate bilayer thickness. Besides, a jump in a local monolayer curvature takes place in this intermediate region, concentrating here most of the elastic stress. This region can participate in a lateral sorting of membrane inclusions by offering them an optimal bilayer thickness and local curvature conditions. In the present study, we consider the sorting of deformable lipid inclusions, undeformable peripheral and deeply incorporated peptide inclusions, and undeformable transmembrane inclusions of different molecular geometry. With rare exceptions, all types of inclusions have an affinity to the ordered domain boundary as compared to the bulk phases. the optimal lateral distribution of inclusions allows relaxing the elastic stress at the boundary of domains.Cellular membranes are laterally heterogeneous 1-3 . Many membrane proteins are believed to function properly only inside lipid-protein domains, also referred to as rafts 4-7 . Proteins in these domains are surrounded by a more or less thick lipid shell [8][9][10][11] . In model purely lipidic systems it is demonstrated that lipids can form similar domains, in which they are in a liquid-ordered (L o ) phase state, while the surrounding membrane is liquid-disordered (L d ) [12][13][14][15] . Ordered domains are usually bilayer, i.e. exist in both membrane leaflets at the same lateral position [14][15][16][17] . Such transbilayer coupling could be driven by elastic deformations arising at the domain boundary and by membrane thermal fluctuations 18-21 . The mechanism of this coupling is not specific to the exact lipid composition of the domain: only the higher ordering of lipids with respect to the surrounding membrane is important [22][23][24] . A bilayer structure of rafts is believed to be a key property in providing raft-dependent signal transduction across the plasma membrane 4,5 . There are increasing evidences that a raft interior itself may be laterally inhomogeneous: some molecules may prefer its boundary region rather than its bulk part. In particular, the fusion peptide of the human immunodeficiency virus (HIV) gp41 protein functions with the highest efficiency only in the presence of the L o /L d phase boundary in the target membrane 25,26 . In addition, the HIV receptor CCR5 preferentially localizes at the domain boundary 26 . It means t...

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“…It is only clear that it requires neither cholesterol nor any other specific lipid or proteinaceous component (7,(9)(10)(11)(12). Most prevalent is the idea that the two leaflets interact at the membrane midplane via overhang.…”

Section: Introductionmentioning

confidence: 99%

Undulations Drive Domain Registration from the Two Membrane Leaflets

Galimzyanov

Kuzmin

Pohl

et al. 2017

Biophysical Journal

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Phase separation in biological membranes plays an important role in protein targeting and transmembrane signaling. Its occurrence in both membrane leaflets commonly gives rise to matching liquid or liquid-ordered domains in the opposing monolayers. The underlying mechanism of such co-localization is not fully understood. The decrease of the line tension around the thicker ordered domain constitutes an important driving force. Yet, robust domain coupling requires an additional energy source, which we have now identified as thermal undulations. Our theoretical analysis of elastic deformations in a lipid bilayer shows that stiffer lipid domains tend to distribute into areas with lower fluctuations of monolayer curvature. These areas naturally align in the opposing monolayers. Thus, coupling requires both membrane leafs to display a heterogeneity in splay rigidities. The heterogeneity may either originate from intrinsic lipid properties or be acquired by adsorption of peripheral molecules. Undulations and line tension act synergistically: the gain in energy due a minimized line tension is proportional to domain radius and thus primarily fuels the registration of smaller domains; whereas the energetic contribution of undulations increases with membrane area and thus primarily acts to coalesce larger domains.

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Metabolic Precursor of Cholesterol Causes Formation of Chained Aggregates of Liquid-Ordered Domains

Cited by 32 publications

References 57 publications

Switching between Successful and Dead-End Intermediates in Membrane Fusion

Switching between Successful and Dead-End Intermediates in Membrane Fusion

Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting

Undulations Drive Domain Registration from the Two Membrane Leaflets

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