The structural basis of cholesterol accessibility in membranes.

Abstract:

:Although the majority of free cellular cholesterol is present in the plasma membrane, cholesterol homeostasis is principally regulated through sterol-sensing proteins that reside in the cholesterol-poor endoplasmic reticulum (ER). In response to acute cholesterol loading or depletion, there is rapid equilibration between the ER and plasma membrane cholesterol pools, suggesting a biophysical model in which the availability of plasma membrane cholesterol for trafficking to internal membranes modulates ER membrane behavior. Previous studies have predominantly examined cholesterol availability in terms of binding to extramembrane acceptors, but have provided limited insight into the structural changes underlying cholesterol activation. In this study, we use both molecular dynamics simulations and experimental membrane systems to examine the behavior of cholesterol in membrane bilayers. We find that cholesterol depth within the bilayer provides a reasonable structural metric for cholesterol availability and that this is correlated with cholesterol-acceptor binding. Further, the distribution of cholesterol availability in our simulations is continuous rather than divided into distinct available and unavailable pools. This data provide support for a revised cholesterol activation model in which activation is driven not by saturation of membrane-cholesterol interactions but rather by bulk membrane remodeling that reduces membrane-cholesterol affinity.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Olsen BN,Bielska AA,Lee T,Daily MD,Covey DF,Schlesinger PH,Baker NA,Ory DS

doi

10.1016/j.bpj.2013.08.042

subject

Has Abstract

pub_date

2013-10-15 00:00:00

pages

1838-47

issue

8

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(13)00989-2

journal_volume

105

pub_type

杂志文章
  • Soft trapping and manipulation of cells using a disposable nanoliter biochamber.

    abstract::Low-power continuous-wave laser radiation is used to form a very stable microbubble at the end of a specially etched and metalized optical fiber probe. We demonstrate that the microbubble, which is firmly attached to the fiber probe, can be used to benignly trap and manipulate living swine sperm cells as well as human...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.105.075614

    authors: Diop M,Taylor R

    更新日期:2006-05-15 00:00:00

  • Stability of the heme environment of the nitric oxide synthase from Staphylococcus aureus in the absence of pterin cofactor.

    abstract::We have used resonance Raman spectroscopy to probe the heme environment of a recently discovered NOS from the pathogenic bacterium Staphylococcus aureus, named SANOS. We detect two forms of the CO complex in the absence of L-arginine, with nu(Fe-CO) at 482 and 497 cm(-1) and nu(C-O) at 1949 and 1930 cm(-1), respective...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.104.042119

    authors: Chartier FJ,Couture M

    更新日期:2004-09-01 00:00:00

  • Calcium transients in cerebellar granule cell presynaptic terminals.

    abstract::Calcium ions act presynaptically to modulate synaptic strength and to trigger neurotransmitter release. Here we detect stimulus-evoked changes in residual free calcium ([Ca2+]i) in rat cerebellar granule cell presynaptic terminals. Granule cell axons, known as parallel fibers, and their associated boutons, were labele...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(95)80398-X

    authors: Regehr WG,Atluri PP

    更新日期:1995-05-01 00:00:00

  • Permeability, phase-boundary potential and conductance in a cholinergic channel without constant field.

    abstract::A potassium-selective, chemically excitable channel, whose characteristics cannot be accurately described by constant-field theory, is studied by a new approach based on diffusion theory but with no need for the classical assumptions of constant field, homogeneous membrane, and equal phase-boundary potentials at both ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(77)85617-8

    authors: Schwartz TL,Kado RT

    更新日期:1977-06-01 00:00:00

  • Chirality-based signatures of local protein environments in two-dimensional optical spectroscopy of two species photosynthetic complexes of green sulfur bacteria: simulation study.

    abstract::Two-dimensional electronic chirality-induced signals of excitons in the photosynthetic Fenna-Matthews-Olson complex from two species of green sulfur bacteria (Chlorobium tepidum and Prosthecochloris aestuarii) are compared. The spectra are predicted to provide sensitive probes of local protein environment of the const...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.108.134387

    authors: Voronine DV,Abramavicius D,Mukamel S

    更新日期:2008-11-15 00:00:00

  • The Roles of Microtubules and Membrane Tension in Axonal Beading, Retraction, and Atrophy.

    abstract::Axonal beading, or the formation of a series of swellings along the axon, and retraction are commonly observed shape transformations that precede axonal atrophy in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. The mechanisms driving these morphological transformations are poorly und...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2019.07.046

    authors: Datar A,Ameeramja J,Bhat A,Srivastava R,Mishra A,Bernal R,Prost J,Callan-Jones A,Pullarkat PA

    更新日期:2019-09-03 00:00:00

  • A cellular screening assay using analysis of metal-modified fluorescence lifetime.

    abstract::Current methods for screening cell receptor internalization often require complex image analysis with limited sensitivity. Here we describe a novel bioassay based on detection of changes in global fluorescence lifetime above a gold substrate, with superresolution axial sensitivity and no need for image analysis. We sh...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2010.03.016

    authors: Cade NI,Fruhwirth G,Archibald SJ,Ng T,Richards D

    更新日期:2010-06-02 00:00:00

  • Field-dependent effect of crown ether (18-crown-6) on ionic conductance of alpha-hemolysin channels.

    abstract::Closing linear poly(ethylene glycol) (PEG) into a circular "crown" dramatically changes its dynamics in the alpha-hemolysin channel. In the electrically neutral crown ether (C2H4O)6, six ethylene oxide monomers are linked into a circle that gives the molecule ion-complexing capacity and increases its rigidity. As with...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.104.044453

    authors: Bezrukov SM,Krasilnikov OV,Yuldasheva LN,Berezhkovskii AM,Rodrigues CG

    更新日期:2004-11-01 00:00:00

  • Limitations of the whole cell patch clamp technique in the control of intracellular concentrations.

    abstract::Recent experimental studies (Pusch and Neher, 1988) and theoretical studies (Oliva et al., 1988) have found that the pipette tip is a significant barrier to diffusion in the whole cell patch clamp configuration. In this paper, we extend the theoretical analysis of fluxes between the pipette and cell to include transme...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(90)82418-8

    authors: Mathias RT,Cohen IS,Oliva C

    更新日期:1990-09-01 00:00:00

  • A unified theory of the B-Z transition of DNA in high and low concentrations of multivalent ions.

    abstract::We showed recently that the high-salt transition of poly[d(G-C)]. poly[d(G-C)] between B-DNA and Z-DNA (at [NaCl] = 2.25 M or [MgCl(2)] = 0.7 M) can be ascribed to the lesser electrostatic free energy of the B form, due to better immersion of the phosphates in the solution. This property was incorporated in cylindrica...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/s0006-3495(00)76665-3

    authors: Guéron M,Demaret J,Filoche M

    更新日期:2000-02-01 00:00:00

  • Effects of hydrostatic pressure on lipid bilayer membranes. II. Activation and reaction volumes of carrier mediated ion transport.

    abstract::Measurements of voltage relaxations following brief charge-pulses applied to lipid bilayers have been performed at different hydrostatic pressures in the presence of the neutral carriers cyclo (D-Val-L-Pro-L-Val-D-Pro)3(PV) and valinomycin. From double-exponential relaxations observed in membranes containing PV-K+ com...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(86)83443-9

    authors: Benz R,Conti F

    更新日期:1986-07-01 00:00:00

  • Pericellular Brush and Mechanics of Guinea Pig Fibroblast Cells Studied with AFM.

    abstract::The atomic force microscopy (AFM) indentation method combined with the brush model can be used to separate the mechanical response of the cell body from deformation of the pericellular layer surrounding biological cells. Although self-consistency of the brush model to derive the elastic modulus of the cell body has be...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2016.06.005

    authors: Dokukin M,Ablaeva Y,Kalaparthi V,Seluanov A,Gorbunova V,Sokolov I

    更新日期:2016-07-12 00:00:00

  • Computational Model of Chimeric Antigen Receptors Explains Site-Specific Phosphorylation Kinetics.

    abstract::Chimeric antigen receptors (CARs) have recently been approved for the treatment of hematological malignancies, but our lack of understanding of the basic mechanisms that activate these proteins has made it difficult to optimize and control CAR-based therapies. In this study, we use phosphoproteomic mass spectrometry a...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2018.08.018

    authors: Rohrs JA,Zheng D,Graham NA,Wang P,Finley SD

    更新日期:2018-09-18 00:00:00

  • Involvement of a heptad repeat in the carboxyl terminus of the dihydropyridine receptor beta1a subunit in the mechanism of excitation-contraction coupling in skeletal muscle.

    abstract::Chimeras consisting of the homologous skeletal dihydropyridine receptor (DHPR) beta1a subunit and the heterologous cardiac/brain beta2a subunit were used to determine which regions of beta1a were responsible for the skeletal-type excitation-contraction (EC) coupling phenotype. Chimeras were transiently transfected in ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.104.043810

    authors: Sheridan DC,Cheng W,Carbonneau L,Ahern CA,Coronado R

    更新日期:2004-08-01 00:00:00

  • Constitutive equations of skeletal muscle based on cross-bridge mechanism.

    abstract::The statistical mechanics of cross-bridge action is considered in order to develop constitutive equations that express fiber tension as a function of degree of activation and time history of speed of contraction. The kinetic equation of A.F. Huxley (1) is generalized to apply to the partially activated state. The rate...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/s0006-3495(85)83895-9

    authors: Tözeren A

    更新日期:1985-02-01 00:00:00

  • Behavior of supercoiled DNA.

    abstract::We study DNA supercoiling in a quantitative fashion by micromanipulating single linear DNA molecules with a magnetic field gradient. By anchoring one end of the DNA to multiple sites on a magnetic bead and the other end to multiple sites on a glass surface, we were able to exert torsional control on the DNA. A rotatin...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(98)77908-1

    authors: Strick TR,Allemand JF,Bensimon D,Croquette V

    更新日期:1998-04-01 00:00:00

  • Whole-embryo modeling of early segmentation in Drosophila identifies robust and fragile expression domains.

    abstract::Segmentation of the Drosophila melanogaster embryo results from the dynamic establishment of spatial mRNA and protein patterns. Here, we exploit recent temporal mRNA and protein expression measurements on the full surface of the blastoderm to calibrate a dynamical model of the gap gene network on the entire embryo cor...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2011.05.060

    authors: Bieler J,Pozzorini C,Naef F

    更新日期:2011-07-20 00:00:00

  • Solutions for transients in arbitrarily branching cables: III. Voltage clamp problems.

    abstract::Branched cable voltage recording and voltage clamp analytical solutions derived in two previous papers are used to explore practical issues concerning voltage clamp. Single exponentials can be fitted reasonably well to the decay phase of clamped synaptic currents, although they contain many underlying components. The ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(93)81039-7

    authors: Major G

    更新日期:1993-07-01 00:00:00

  • Binding of cations of group IA and IIA to bovine serum amine oxidase: effect on the activity.

    abstract::In this paper, we report on the presence of cation binding areas on bovine serum amine oxidase, where metal ions of the groups IA and IIA, such as Na(+), K(+), Cs(+), Mg(2+), and Ca(2+), bind with various affinities. We found a cation-binding area that influences the enzyme activity if occupied, so that the catalytic ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(02)73983-0

    authors: Di Paolo ML,Scarpa M,Corazza A,Stevanato R,Rigo A

    更新日期:2002-10-01 00:00:00

  • Exploring the ion selectivity properties of a large number of simplified binding site models.

    abstract::The ability to discriminate between different cations efficiently is essential for the proper physiological functioning of many membrane transport proteins. One obvious mechanism of ion selectivity is when a binding site is structurally constrained by the protein architecture and its geometry is precisely adapted to f...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2010.03.038

    authors: Roux B

    更新日期:2010-06-16 00:00:00

  • Large-scale rotational motions of proteins detected by electron paramagnetic resonance and fluorescence.

    abstract::Direct spectroscopic measurements of rotational motions of proteins and large protein segments are crucial to understanding the molecular dynamics of protein function. Fluorescent probes and spin labels attached to proteins have proved to be powerful tools in the study of large-scale protein motions. Fluorescence depo...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(78)85394-6

    authors: Thomas DD

    更新日期:1978-11-01 00:00:00

  • Effect of nonuniform interstitial space properties on impulse propagation: a discrete multidomain model.

    abstract::This work presents a discrete multidomain model that describes ionic diffusion pathways between connected cells and within the interstitium. Unlike classical models of impulse propagation, the intracellular and extracellular spaces are represented as spatially distinct volumes with dynamic/static boundary conditions t...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.108.137349

    authors: Roberts SF,Stinstra JG,Henriquez CS

    更新日期:2008-10-01 00:00:00

  • Dynamic properties of the haptenic site of lipid haptens in phosphatidylcholine membranes. Their relation to the phase transition of the host lattice.

    abstract::The relation between the dynamic properties of the haptenic site of lipid haptens and the phase transition of the host lattice was investigated using head group spin-labeled phosphatidylethanolamines, that is, spin-label lipid haptens (Brûlet, P., and H. M. McConnell, 1976, Proc. Natl. Acad. Sci. USA., 73:2977-2981; B...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(87)83206-X

    authors: Takeshita K,Utsumi H,Hamada A

    更新日期:1987-08-01 00:00:00

  • A physical model of ATP-induced actin-myosin movement in vitro.

    abstract::The nature of the mechanism limiting the velocity of ATP-induced unidirectional movements of actin-myosin filaments in vitro is considered. In the sliding process two types of "cyclic" interactions between myosin heads and actin are involved, i.e., productive and nonproductive. In the productive interaction, myosin he...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(91)82228-7

    authors: Tawada K,Sekimoto K

    更新日期:1991-02-01 00:00:00

  • Structural effects of an LQT-3 mutation on heart Na+ channel gating.

    abstract::Computational methods that predict three-dimensional structures from amino acid sequences have become increasingly accurate and have provided insights into structure-function relationships for proteins in the absence of structural data. However, the accuracy of computational structural models requires experimental app...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(04)74251-4

    authors: Tateyama M,Liu H,Yang AS,Cormier JW,Kass RS

    更新日期:2004-03-01 00:00:00

  • Simultaneous tether extraction from endothelial cells and leukocytes: observation, mechanics, and significance.

    abstract::It has been hypothesized, from earlier studies on single-tether extraction from individual leukocytes and human umbilical vein endothelial cells, that during rolling of leukocytes on the endothelium, simultaneous extraction of membrane nanotubes (tethers) occurs, resulting in enhancement of the force decrease on the a...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.107.109298

    authors: Girdhar G,Shao JY

    更新日期:2007-12-01 00:00:00

  • Proteins in membrane mimetic systems. Insertion of myelin basic protein into microemulsion droplets.

    abstract::The insertion of myelin basic protein into microemulsion droplets of sodium bis (2-ethylhexyl) sulfosuccinate (AOT) has been studied by quasi-elastic light scattering. Measurements were made at both low and high molar ratios of water to surfactant, as a function of protein occupancy. The hydrodynamic radii of filled a...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(85)83851-0

    authors: Chatenay D,Urbach W,Cazabat AM,Vacher M,Waks M

    更新日期:1985-12-01 00:00:00

  • The equation of motion for sperm flagella.

    abstract::The equation of motion for sperm flagella, in which the elastic bending moment and the active contractile moment are balanced by the moment from the viscous resistance of the surrounding fluid, is solved for a wave solution that superimposes partial solutions. Substitution of the expression for the wave solution into ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(78)85442-3

    authors: Rikmenspoel R

    更新日期:1978-08-01 00:00:00

  • Use of protein database for the computation of the dipole moments of normal and abnormal hemoglobins.

    abstract::Previously, we discussed the calculation of the dipole moments of small proteins using the three-dimensional protein data-base. Our results demonstrate that the calculated dipole moments are in acceptable agreement with measured values. We, however, noted the difficulty of the calculation with larger proteins, in part...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(93)81524-8

    authors: Takashima S

    更新日期:1993-05-01 00:00:00

  • Investigation of the adsorption of PEG1500-12-acyloxystearate surfactants onto phospholipid bilayers: an ellipsometry and cryo-TEM study.

    abstract::In this article we present a study of a new class of surfactants denoted as PEG1500-12-acyloxystearates, which have potential use as pharmaceutical solubilizers. These amphiphilic molecules present interesting properties with regard to cell damage effects. PEG1500-12-acyloxystearates with C(14) to C(16) acyloxy chains...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.107.109900

    authors: Vaccaro M,von Corswant C,Söderman O

    更新日期:2007-12-15 00:00:00