Elasticity of the Lipid Bilayer Edge. Trends in Line Tension

SummaryBax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. They may embed in the cytosolic leaflet of the lipid bilayer generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, they may comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determine a high-resolution structure of the Bax core region that forms a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but creating polar interactions between charged residues and lipid heads. Structure-guided mutations demonstrate the importance of both protein-lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria.

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Calculation of line tension in various models of lipid bilayer pore edge

Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology ◽

10.1134/s1990747809020160 ◽

2009 ◽

Vol 3 (2) ◽

pp. 223-230 ◽

Cited By ~ 4

Author(s):

R. J. Molotkovsky ◽

S. A. Akimov

Keyword(s):

Lipid Bilayer ◽

Line Tension

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NRas slows the rate at which a model lipid bilayer phase separates

Faraday Discussions ◽

10.1039/c3fd00131h ◽

2014 ◽

Vol 169 ◽

pp. 209-223 ◽

Cited By ~ 14

Author(s):

Elizabeth Jefferys ◽

Mark S. P. Sansom ◽

Philip W. Fowler

Keyword(s):

Lipid Bilayer ◽

Cell Signalling ◽

Line Tension ◽

Structural Data ◽

Coarse Grained ◽

Ras Proteins ◽

C Terminus ◽

Ras Family ◽

Multiple Copies ◽

Dynamics Simulations

The Ras family of small membrane-associated GTP-ases are important components in many different cell signalling cascades. They are thought to cluster on the cell membrane through association with cholesterol-rich nanodomains. This process remains poorly understood. Here we test the effect of adding multiple copies of NRas, one of the canonical Ras proteins, to a three-component lipid bilayer that rapidly undergoes spinodal decomposition (i.e.unmixing), thereby creating ordered and disordered phases. Coarse-grained molecular dynamics simulations of a large bilayer containing 6000 lipids, with and without protein, are compared. NRas preferentially localises to the interface between the domains and slows the rate at which the domains grow. We infer that this doubly-lipidated cell signalling protein is reducing the line tension between the ordered and disordered regions. This analysis is facilitated by our use of techniques borrowed from image-processing. The conclusions above are contingent upon several assumptions, including the use of a model lipid with doubly unsaturated tails and the limited structural data available for the C-terminus of NRas, which is where the lipid anchors are found.

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Lateral tension increases the line tension between two domains in a lipid bilayer membrane

Physical Review E ◽

10.1103/physreve.75.011919 ◽

2007 ◽

Vol 75 (1) ◽

Cited By ~ 61

Author(s):

Sergey A. Akimov ◽

Peter I. Kuzmin ◽

Joshua Zimmerberg ◽

Fredric S. Cohen

Keyword(s):

Lipid Bilayer ◽

Line Tension ◽

Bilayer Membrane ◽

Lipid Bilayer Membrane ◽

Lateral Tension

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Atomistic Simulation of Pore Formation in Lipid Bilayers in the Presence of Dimethylsulfoxide: Further Evidence for Entropic Driven Pore Formation

ASME 2008 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2008-192793 ◽

2008 ◽

Author(s):

Raghava Alapati ◽

Dorel Moldovan ◽

Ram Devireddy

Keyword(s):

Lipid Bilayer ◽

Lipid Bilayers ◽

Pore Formation ◽

Configurational Entropy ◽

Line Tension ◽

Nucleation Theory ◽

Classical Nucleation Theory ◽

Pore Shape ◽

Dmso Concentration ◽

Pore Nucleation

In a recent study, Moldovan et al [1] have demonstrated that in the presence of 11.3 mol% dimethylsulfoxide (DMSO) a pore can nucleate and grow spontaneously in a lipid bilayer even in the absence of an externally applied stresses or electric field. The authors rationalized the spontaneous pore nucleation, in the absence of any external driving force, by considering the combined effect of the entropy of pore shape fluctuation and the significant decrease of the bilayer line tension in the presence of DMSO. Building on the classical nucleation theory developed three decades ago by Lister [2] the authors propose a new formulation for the bilayer free energy that incorporates the pore shape configurational entropy. According to this study, in the presence of DMSO, the pore nucleates spontaneously and grows provided the bilayer line tension decreases below a threshold value, λ. In this study we report our recent simulation results on the effect of DMSO concentration on both bilayer line tension and bilayer structural stability with respect to pore nucleation. The lipid bilayer systems investigated in this study by molecular dynamics (MD) consists of 96 molecules (48 in each leaflet) of dimyristoylphosphatidylcholine (DMPC) immersed in DMSO-water solutions at various concentrations. In all MD simulations reported the bilayer systems were followed over 100 ns. Our simulations results indicate the existence of a critical DMSO concentration below which there are no pores nucleated in the lipid bilayers. Our findings corroborate and complement the entropy-based pore nucleation model proposed earlier by Moldovan et al. [1].

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Dynamics of finite size lipid bilayer. Narrowing of bilayer edge induced by its non-linear elastic properties

The Journal of Physical Chemistry ◽

10.1021/j100041a054 ◽

1995 ◽

Vol 99 (41) ◽

pp. 15298-15303 ◽

Cited By ~ 2

Author(s):

Antonio Raudino

Keyword(s):

Lipid Bilayer ◽

Elastic Properties ◽

Finite Size ◽

Linear Elastic ◽

Non Linear ◽

Bilayer Edge

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Interpretation of Phase Boundary Fluctuation Spectra in Biological Membranes with Nanoscale Organization

10.1101/746800 ◽

2019 ◽

Author(s):

S. S. Iyer ◽

A. Negi ◽

A. Srivastava

Keyword(s):

Lipid Bilayer ◽

Gaussian Function ◽

Line Tension ◽

Wave Theory ◽

Coarse Grained ◽

Support Vector ◽

Resolution Limit ◽

Point Spread Functions ◽

Power Spectral

AbstractIn this work, we use Support Vector Machine algorithm to detect simple and complex interfaces in atomistic and coarse-grained molecular simulation trajectories of phase separating lipid bilayer systems. We show that the power spectral density of the interfacial height fluctuations and in turn the line tension of the lipid bilayer systems depend on the order parameter used to identify the intrinsic interface. To highlight the effect of artificial smoothing of the interface on the fluctuation spectra and the ensuing line tension calculations, we perform a convolution of the boundaries identified at molecular resolution with a 2D Gaussian function of variance ε2 equal to the resolution limit, (1/2πε2)exp(−|r|2/2ε2). The convolution function is given by h⊗g, where h is the instantaneous height fluctuation and g is the Gaussian function. This is similar to the effect of point spread functions in experiments. We find that the region of fluctuation spectra that scales according to capillary wave theory formalism depends on the complexity of the interfacial geometry, which may not always be detected at experimental resolutions. We propose that the different q-regimes in the fluctuation spectra can be used to characterize mode dependent inter-facial tensions to understand the interfaces beyond the linear line tension calculations. This could also be useful in interpretation of fluctuating boundaries in out-of-equilibrium in-vivo membrane systems that carry information about the nature of non-thermal (active) fluctuations in these systems.

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