Mechanical Properties of Nanoscopic Lipid Domains

Nickels, Jonathan D.; Cheng, Xiaolin; Mostofian, Barmak; Stanley, Christopher B.; Lindner, Benjamin; Heberle, Frederick A.; Perticaroli, Stefania; Feygenson, Mikhail; Egami, T.; Standaert, Robert F.; Smith, Jeremy C.; Myles, Dean A. A.; Ohl, Michael; Katsaras, John

doi:10.1021/jacs.5b08894

Cited by 109 publications

(155 citation statements)

References 94 publications

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“…By matching the NSLD of the solvent to all of the head groups and the acyl region of one phase, it is possible to isolate the acyl chains of the other phase, as depicted in Fig 4. Studying the scattering of individual phases provides a range of new possibilities. For example, by examining the acyl thickness of individual phases, it was determined that nanodomains in the POPC/DSPC/cholesterol system are in register, or aligned across the two bilayer leaflets 53 . For antiregistered phases, one would expect to see only a monolayer thickness due to the apposition of visible Ld phase and the invisible Lo phase.…”

Section: Small Angle Neutron Scattering (Sans)mentioning

confidence: 99%

“…However, lipid mixtures emulating the inner leaflet fail to do so, remaining uniformly mixed 50,51 . This is intriguing because rafts are expected to exist in both leaflets of the bilayer 49,52,53 , implying a critical role of inter-leaflet coupling in vivo. Moreover, the mechanisms by which the outer leaflet of the bilayer could interact with the inner leaflet remain unknown.…”

Section: Introductionmentioning

confidence: 99%

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Lateral organization, bilayer asymmetry, and inter-leaflet coupling of biological membranes

Nickels

Smith

Cheng

2015

Chemistry and Physics of Lipids

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108

115

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Understanding of cell membrane organization has evolved significantly from the classic fluid mosaic model. It is now recognized that biological membranes are highly organized structures, with differences in lipid compositions between inner and outer leaflets and in lateral structures within the bilayer plane, known as lipid rafts. These organizing principles are important for protein localization and function as well as cellular signaling. However, the mechanisms and biophysical basis of lipid raft formation, structure, dynamics and function are not clearly understood. One key question, which we focus on in this review, is how lateral organization and leaflet compositional asymmetry are coupled. Detailed information elucidating this question has been sparse because of the small size and transient nature of rafts and the experimental challenges in constructing asymmetric bilayers. Resolving this mystery will require advances in both experimentation and modeling. We discuss here the preparation of model systems along with experimental and computational approaches that have been applied in efforts to address this key question in membrane biology. We seek to place recent and future advances in experimental and computational techniques in context, providing insight into in-plane and transverse organization of biological membranes.

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Section: Small Angle Neutron Scattering (Sans)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lateral organization, bilayer asymmetry, and inter-leaflet coupling of biological membranes

Nickels

Smith

Cheng

2015

Chemistry and Physics of Lipids

Self Cite

108

115

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“…Neutrons have wavelengths on the order of Ångstroms (Å) and are thus inherently nanoscopic probes, well-matched to the dimensions of membrane structure. Using appropriately designed experiments, both transverse (normal to the membrane plane)[7] and lateral (within the membrane plane)[28,29] structure can be accurately determined. Importantly, neutron-scattering techniques do not require extrinsic molecules or heavy atoms as labels and rely instead on hydrogen (H)/deuterium (D) isotopic substitution.…”

Section: Introductionmentioning

confidence: 99%

The in vivo structure of biological membranes and evidence for lipid domains

et al. 2017

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Examining the fundamental structure and processes of living cells at the nanoscale poses a unique analytical challenge, as cells are dynamic, chemically diverse, and fragile. A case in point is the cell membrane, which is too small to be seen directly with optical microscopy and provides little observational contrast for other methods. As a consequence, nanoscale characterization of the membrane has been performed ex vivo or in the presence of exogenous labels used to enhance contrast and impart specificity. Here, we introduce an isotopic labeling strategy in the gram-positive bacterium Bacillus subtilis to investigate the nanoscale structure and organization of its plasma membrane in vivo. Through genetic and chemical manipulation of the organism, we labeled the cell and its membrane independently with specific amounts of hydrogen (H) and deuterium (D). These isotopes have different neutron scattering properties without altering the chemical composition of the cells. From neutron scattering spectra, we confirmed that the B. subtilis cell membrane is lamellar and determined that its average hydrophobic thickness is 24.3 ± 0.9 Ångstroms (Å). Furthermore, by creating neutron contrast within the plane of the membrane using a mixture of H- and D-fatty acids, we detected lateral features smaller than 40 nm that are consistent with the notion of lipid rafts. These experiments—performed under biologically relevant conditions—answer long-standing questions in membrane biology and illustrate a fundamentally new approach for systematic in vivo investigations of cell membrane structure.

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“…33,34,39–41 In particular, SANS has revealed the size and physical properties of nanoscale domains in DSPC/CHOL/POPC large unilamellar vesicles. 40,43 Due to the size (~15 nm from SANS and FRET) of these domains and the prevalence of POPC in the plasma membrane of mammalian cells, these mixtures may represent a more accurate model for lipid rafts. 33,41 However, they remain challenging to study due to the lack of methods for studying nanoscale domains.…”

Section: Resultsmentioning

confidence: 99%

Atomic Recombination in Dynamic Secondary Ion Mass Spectrometry Probes Distance in Lipid Assemblies: A Nanometer Chemical Ruler

Moss

Boxer

2016

J. Am. Chem. Soc.

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The lateral organization of biological membranes is thought to take place on the nanometer length scale. However, this length scale and the dynamic nature of small lipid and protein domains have made characterization of such organization in biological membranes and model systems difficult. Here we introduce a new method for measuring the colocalization of lipids in monolayers and bilayers using stable isotope labeling. We take advantage of a process that occurs in dynamic SIMS called atomic recombination, in which atoms on different molecules combine to form diatomic ions that are detected with a NanoSIMS instrument. This process is highly sensitive to the distance between molecules. By measuring the efficiency of the formation of 13C15N− ions from 13C and 15N atoms on different lipid molecules, we measure variations in the lateral organization of bilayers even though these heterogeneities occur on a length scale of only a few nm, well below the diameter of the primary ion beam of the NanoSIMS instrument or even the best super-resolution fluorescence methods. Using this technique, we provide direct evidence for nanoscale phase separation in a model membrane, which may provide a better model for the organization of biological membranes than lipid mixtures with microscale phase separation. We expect this technique to be broadly applicable to any assembly where very short scale proximity is of interest or unknown, both in chemical and biological systems.

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Mechanical Properties of Nanoscopic Lipid Domains

Cited by 109 publications

References 94 publications

Lateral organization, bilayer asymmetry, and inter-leaflet coupling of biological membranes

Lateral organization, bilayer asymmetry, and inter-leaflet coupling of biological membranes

The in vivo structure of biological membranes and evidence for lipid domains

Atomic Recombination in Dynamic Secondary Ion Mass Spectrometry Probes Distance in Lipid Assemblies: A Nanometer Chemical Ruler

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