Influence of DPH on the Structure and Dynamics of a DPPC Bilayer

Repáková, Jarmila; Holopainen, Juha M.; Morrow, Michael R.; McDonald, Mark; Čapková, Pavla; Vattulainen, Ilpo

doi:10.1529/biophysj.104.055533

Cited by 112 publications

(102 citation statements)

References 54 publications

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“…DPH displays equal partitioning between both phases. Moreover, perturbations induced by DPH are weak and of local nature and do not affect thermotropic behavior in any significant manner (43). In the 12-SLPC domain, DPH fluorescence is quenched but DPH molecules remaining in the DPPC-rich domain have a low probability of interacting with quencher molecules and give higher fluorescence intensity.…”

Section: Effects Of Desmosterol and Cholesterol On The Formation And mentioning

confidence: 99%

Significance of Sterol Structural Specificity

Vainio

Jansen

Koivusalo

et al. 2006

Journal of Biological Chemistry

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124

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Desmosterol is an immediate precursor of cholesterol in the Bloch pathway of sterol synthesis and an abundant membrane lipid in specific cell types. The significance of the difference between the two sterols, an additional double bond at position C24 in the tail of desmosterol, is not known. Here, we provide evidence that the biophysical and functional characteristics of the two sterols differ and that this is because the double bond at C24 significantly weakens the sterol ordering potential. In model membranes, desmosterol was significantly weaker than cholesterol in promoting the formation or stability of ordered domains, and in mammalian cell membranes, desmosterol associated less avidly than cholesterol with detergentresistant membranes. Atomic scale molecular dynamics simulations showed that the double bond gives rise to additional stress in the tail, creating a rigid structure between C24 and C27 and favoring tilting of desmosterol distinct from cholesterol. Functional effects of desmosterol in cell membranes were assessed upon acutely exchanging ϳ70% of cholesterol to desmosterol. This led to impaired raft-dependent signaling via the insulin receptor, whereas non-raft-dependent protein secretion was not affected. We suggest that the choice of cholesterol synthesis route may provide a physiological mechanism to modulate raft-dependent functions in cells.In model membranes, cholesterol associates preferentially with long, saturated acyl chains, such as those in sphingolipids, thus reducing the area per lipid molecule (1, 2). There is substantial evidence to suggest that ordered lipid domains (rafts) composed of sterol and saturated lipids also exist in eukaryotic cell membranes and play important roles in numerous biological processes (3, 4). Lipid rafts are considered to exist in a liquid-ordered (L o ) 2 state characterized by tight ordering but relatively high lateral mobility of lipids and operationally often defined as detergent-resistant membranes (DRMs) (5, 6). Instead, unsaturated phospholipids are loosely packed, forming a liquid-disordered (L d ) membrane that is solubilized upon the addition of mild detergents. At least in model membranes, cholesterol is able to promote the separation of L o and L d domains (7-9). In cells, cholesterol levels influence the domain partitioning and biological activity of proteins that co-isolate in detergent-resistant membranes (DRMs) (10, 11).Taking the postulated critical role for cholesterol in raft formation and the diversity of sterols in biological materials, the sterol structural requirements for promoting ordered domain formation are highly relevant. Until now, the effects of sterol/steroid structure have mostly been addressed in model membranes. Slight modifications of the cholesterol structure (e.g. a shift of the double bond in the sterol ring or alteration of the 3-OH group) change the domain-forming properties of the molecule (12-14). Among the structurally closest relatives of cholesterol are its immediate biosynthetic precursors. The only difference ...

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Section: Effects Of Desmosterol and Cholesterol On The Formation And mentioning

confidence: 99%

Significance of Sterol Structural Specificity

Vainio

Jansen

Koivusalo

et al. 2006

Journal of Biological Chemistry

Self Cite

124

View full text Add to dashboard Cite

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“…All simulations were performed at a temperature of 323K which is above the main phase transition temperature of the DPPC bilayer (314K). 33 All molecular species were independently coupled to the Nosé-Hoover thermostat 34,35 with a coupling time constant of 0.5 ps. The system's volume was allowed to fluctuate according to the semi-isotropic pressure coupling method.…”

Section: Force Field and Simulation Parametersmentioning

confidence: 99%

Effect of arginine-rich cell penetrating peptides on membrane pore formation and life-times: a molecular simulation study

Sun

Forsman

Lund

et al. 2014

Phys. Chem. Chem. Phys.

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Link to publicationCitation for published version (APA): Sun, D., Forsman, J., Lund, M., & Woodward, C. E. (2014). Effect of arginine-rich cell penetrating peptides on membrane pore formation and life-times: a molecular simulation study. Physical Chemistry Chemical Physics, 16(38), 20785-20795. https://doi.org/10.1039/c4cp02211d General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. 2 AbstractThe molecular basis for the effectiveness of arginine-rich cell penetrating peptides (ARCPPs) traversing cell membrane barrier is not well established. The fact that a threshold concentration of ARCPPs is required for efficient translocation in model membranes suggests cooperative action by ARCPPs. We used umbrella sampling simulations to calculate the free energies for membrane pore formation. The membrane-bound octaarginine (ARG8) peptides showed little cooperativity in lowering the free energy barrier to generate membrane pores by direct peptide translocation or by lipid flip-flop. Instead, high concentrations of ARG8 peptides were found to expand the surface area of the lipid bilayer due to the deep partitioning of guanidinium ions into the lipid glycerol regions. Surface-bound ARG8 peptides can also insert the arginine side chain into one existing transient membrane pore, and the lifetime of the transient membrane pore is significantly extended by arginine. This suggests a cooperative kinetic mechanism may act above a threshold adsorption concentration to facilitate the rapid uptake of these peptides.3

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“…The effects are prominent but as in most other local in nature, i.e., the changes observed in the properties of lipid molecules are significant in the vicinity of DPH, but reduce rapidly as the distance from the probe increases in agreement with DSC and NMR data. DSC shows only subtle perturbation to the cooperative behavior of the membrane system in the presence of DPH, and 2 H NMR shows that DPH gives rise to a slight increase in the lipid chain order [75].…”

Section: Fluorescent Probesmentioning

confidence: 94%

“…Repáková et al presented a very thorough study of the behavior and perturbations of DPH(1,6-diphenyl-1,3,5-hexatriene) in a DPPC bilayer [74,75]. They employed 50 ns molecular dynamics simulations -which was very long at the time -to study the distribution, orientation, and dynamics of DPH fluorescent probes.…”

Section: Fluorescent Probesmentioning

confidence: 99%

Molecular modeling of lipid probes and their influence on the membrane

Faller

2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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In this review a number of Molecular Dynamics simulation studies are discussed which focus on the understanding of the behavior of lipid probes in biomembranes. Experiments often use specialized probe moieties or molecules to report on the behavior of a membrane and try to gain information on the membrane as a whole from the probe lipids as these probes are the only things an experiment sees. Probes can be used to make NMR, EPR and fluorescence accessible to the membrane and use fluorescent or spin-active moieties for this purpose. Clearly membranes with and without probes are not identical which makes it worthwhile to elucidate the differences between them with detailed atomistic simulations. In almost all cases these differences are confined to the local neighborhood of the probe molecules which are sparsely used and generally present as single molecules. In general, the behavior of the bulk membrane lipids can be qualitatively understood from the probes but in most cases their properties cannot be directly quantitatively deduced from the probe behavior.

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Influence of DPH on the Structure and Dynamics of a DPPC Bilayer

Cited by 112 publications

References 54 publications

Significance of Sterol Structural Specificity

Significance of Sterol Structural Specificity

Effect of arginine-rich cell penetrating peptides on membrane pore formation and life-times: a molecular simulation study

Molecular modeling of lipid probes and their influence on the membrane

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