Adaptive Lipid Packing and Bioactivity in Membrane Domains

Sezgin, Erdinç; Gutmann, Theresia; Buhl, Tomasz; Dirkx, Ronald; Grzybek, Michał; Coskun, Ünal; Solimena, Michele; Simons, Kai; Levental, Ilya; Schwille, Petra

doi:10.1371/journal.pone.0123930

Cited by 108 publications

(119 citation statements)

References 45 publications

(63 reference statements)

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“…This more heterogeneous view is in agreement with the findings of recent fluorescent imaging experiments (Kaiser et al, 2009;Sezgin et al, 2015).…”

Section: Automated System Generationsupporting

confidence: 92%

“…Using a variety of membrane and lipid imaging methods -such as AFM, nuclear magnetic resonance (NMR), X-ray, mass spectrometry and spectroscopy (Holthuis and Menon, 2014;Jacobson et al, 2007;Kaiser et al, 2009;Klose et al, 2012;Marsh, 2013;Sampaio et al, 2011;Sezgin et al, 2015;van Meer et al, 2008) -much has been learned with regard to cellular membranes, including their heterogeneous nature. However, the detailed lipid organization of these membranes remains elusive, and important questions remain, including what are the individual roles of all these lipids, and how do they interact and organize in the membrane plane?…”

Section: Automated System Generationmentioning

confidence: 99%

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Computational ‘microscopy’ of cellular membranes

Ingólfsson

Arnarez²,

Periole³

et al. 2016

Journal of Cell Science

134

120

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Computational 'microscopy' refers to the use of computational resources to simulate the dynamics of a molecular system. Tuned to cell membranes, this computational 'microscopy' technique is able to capture the interplay between lipids and proteins at a spatiotemporal resolution that is unmatched by other methods. Recent advances allow us to zoom out from individual atoms and molecules to supramolecular complexes and subcellular compartments that contain tens of millions of particles, and to capture the complexity of the crowded environment of real cell membranes. This Commentary gives an overview of the main concepts of computational 'microscopy' and describes the state-of-the-art methods used to model cell membrane processes. We illustrate the power of computational modelling approaches by providing a few in-depth examples of largescale simulations that move up from molecular descriptions into the subcellular arena. We end with an outlook towards modelling a complete cell in silico.

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“…This more heterogeneous view is in agreement with the findings of recent fluorescent imaging experiments (Kaiser et al, 2009;Sezgin et al, 2015).…”

Section: Automated System Generationsupporting

confidence: 92%

Section: Automated System Generationmentioning

confidence: 99%

Computational ‘microscopy’ of cellular membranes

Ingólfsson

Arnarez²,

Periole³

et al. 2016

Journal of Cell Science

134

120

View full text Add to dashboard Cite

show abstract

“…11 to such systems is suspect, however, as the magnitude of the bending rigidity variation is well beyond the applicability of second-order perturbation theory; we return to this point below. Furthermore, with regard to in vivo systems, although the differences in, e.g., lipid packing (and presumably bending rigidity variations) between the raft and non-raft phases are smaller than those in simple ternary ones (27), it is plausible that membrane undulations contribute to co-localization of sufficiently large domains ðRT5' $ 25 nmÞ, given the rather modest bending rigidity heterogeneity, dkz50:25 k 0 , required for the mechanism to be relevant.…”

Section: Case Ii: Partially Co-localized Domainsmentioning

confidence: 99%

Lipid Domain Co-localization Induced by Membrane Undulations

Haataja

2017

Biophysical Journal

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Multicomponent lipid bilayer membranes display rich phase transition and associated compositional lipid domain formation behavior. When both leaflets of the bilayer contain domains, they are often found co-localized across the leaflets, implying the presence of a thermodynamic interleaflet coupling. In this work, it is demonstrated that fluctuation-induced interactions between domains embedded within opposing membrane leaflets provide a robust means to co-localize the domains. In particular, it is shown via a combination of a mode-counting argument, a perturbative calculation, and a non-perturbative treatment of a special case, that spatial variations in membrane bending rigidity associated with lipid domains embedded within the background phase always lead to an attractive interleaflet coupling with a magnitude of $ 0:01 k B T=nm 2 in simple model membrane systems. Finally, it is demonstrated that the fluctuation-induced coupling is very robust against membrane tension and substrate interactions.

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“…The Laurdan generalized polarization (GP) measurement gives degrees of order state of hydrophobic carbon chains of phospholipid molecule. 8,9 The wavelength of the fluorescent emission from Laurdan is affected by the number of water molecules near Laurdan. The fluorescent spectrum shifts toward longer wavelengths due to dipole relaxation.…”

mentioning

confidence: 99%

Destabilization of Phase-separated Structures in Local Anesthetic-containing Model Biomembranes

2015

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We observed the phase behaviors, and the changes of membrane fluidity in lipid membranes containing local anesthetics (LAs), lidocaine and tetracaine. The phase separation in DOPC/DPPC binary membranes had not been changed significantly by addition of LAs, whereas that in DOPC/DPPC/ Chol ternary membranes was suppressed by LAs. In order to evaluate the membrane fluidity, Laurdan generalized polarization values of membranes were measured. The fluidity of DOPC-rich phase in the ternary membrane became lower as LAs concentration had increased. Our results indicated the correlation between physical property change on membrane and pharmacological functions of LAs.Local anesthetics (LAs) are essential drugs for modern medicine that are often used to suppress patients' pain. LAs are known to target functional proteins, voltage-dependent sodium channels, which are located on cellular membranes. The mechanism how LAs shield pain signals was believed to be that LAs interact with the channel protein directly, and deactivate it.1 However, binding sites on the channel proteins had not been elucidated completely. In addition, according to past reports, LAs exhibit toxicity against human cells. The presence of LAs sometimes induces fatal side effects such as allergy, liver malfunction, and analgesia. 2 The mechanisms by which these side effects are induced by LAs are also not fully understood. Recently, however, some groups are expecting that these mechanisms can be explained by the change of the physical properties of lipid membranes where the proteins are buried induced by addition of LAs. 3Cell membranes, which are composed of lipid bilayer structure, are known to relate with signal transductions via membrane dynamics such as vesicular formation. In fact, some studies are providing correlation between physical property changes on biomembrane and behavior of channel proteins. 4 Moreover, a "lipid raft model" was proposed by Simons and Ikonen in 1997. 5,6 Lipid raft is a region where a large amount of saturated lipids and cholesterols are included and some functional molecules such as ion channels and membrane receptors can be localized, and lipid raft is speculated as a platform for signal transduction.In order to reveal the mechanism of raft formation, liposome, which is mainly composed of phospholipids, is used as a mimetic model of a biomembrane system. Liposome has similar structure to actual biomembranes, so we can directly observe similar phenomena on liposome with optical microscopy. Especially, raft formation can be regarded as the phase separation between saturated lipid and cholesterol-rich and unsaturated lipid-rich phases in a model membrane system, so from a biological aspect, it is important to discuss phase behavior of model membrane. 7In this study, we observed the phase separation in lipid membranes containing typical LAs, lidocaine and tetracaine, by optical microscopy. In order to understand the phase separation, the membrane fluidity is estimated by Laurdan generalized polarization measurement. Finally, w...

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Adaptive Lipid Packing and Bioactivity in Membrane Domains

Cited by 108 publications

References 45 publications

Computational ‘microscopy’ of cellular membranes

Computational ‘microscopy’ of cellular membranes

Lipid Domain Co-localization Induced by Membrane Undulations

Destabilization of Phase-separated Structures in Local Anesthetic-containing Model Biomembranes

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