L<SUB>&#946;'</SUB>&#8594;L<SUB>c'</SUB> phase transition in phosphatidylcholine lipid bilayers: a disorder-order transition in two dimensions

The structure of the Lc' phase exhibited by hydrated dipalmitoylphosphatidylcholine (DPPC) was recently determined by Raghunathan and Katsaras [Phys. Rev. Lett. 74, 4456 (1995)] from x-ray diffraction studies on oriented multibilayers. Here, we reanalyze the powder diffraction data reported in the literature on a number of hydrated lipids possessing the phosphatidylcholine headgroup. As in DPPC, the Lc' phase in all of these systems is found to be characterized by two-dimensional ordering of the lipid molecules on a superlattice of the hydrocarbon chain lattice. We also discuss the influence of headgroup interactions on the structure of this phase

Structure of the ripple phase in chiral and racemic dimyristoylphosphatidylcholine multibilayers

We present electron density maps of the ripple phase of chiral and racemic dimyristoylphosphatidylcholine. The structures of the two systems are found to be identical within experimental errors, thus unambiguously showing that the chirality of the lipid molecules does not influence the structure of this phase

Structure and hydration of phytoglycogen nanoparticles: Nature\u27s dendrimer

Nature offers amazing examples of nanostructured molecules and materials. I will focus on phytoglycogen, a highly-branched polymer of glucose produced in the form of dense, monodisperse nanoparticles by some varieties of plants such as sweet corn. The particles are chemically simple, but have a special dendrimeric or tree-like structure that produces interesting and unusual properties such as extraordinary water retention, and low viscosity and exceptional stability in water. These properties point to a wide variety of potential applications from cosmetics to drug delivery, yet these applications need to be enabled by a deeper understanding of the unique structure of the particles and their interaction with water. To achieve this, we have used a wide range of techniques. Neutron scattering has revealed that the nanoparticles have uniform size and density and are highly hydrated, with each nanoparticle containing about 250% of its mass in water [1]. Surface-sensitive infrared absorption measurements on phytoglycogen films show that the high degree of branching in phytoglycogen leads to a well ordered “network” structure of the hydration water within the particles [2]. Rheology measurements have revealed weak interactions between the particles, allowing loading of the particles into water up to 20% w/w before significant increases in viscosity are observed, showing that this is an interesting model system for studying soft colloid physics [3]. Taken together, these studies provide new insights that are key to fully understanding and exploiting these materials in new technologies and therapies. [1] J.D. Nickels, J. Atkinson, E. Papp-Szabo, C. Stanley, S.O. Diallo, S. Perticaroli, B. Baylis, P. Mahon, G. Ehlers, J. Katsaras and J.R. Dutcher. Structure and Hydration of Highly-Branched, Monodisperse Phytoglycogen Nanoparticles, Biomacromolecules 17, 735-743 (2016). [2] M. Grossutti and J.R. Dutcher. Correlation Between Chain Architecture and Hydration Water Structure in Polysaccharides, Biomacromolecules 17, 1198-1204 (2016). [3] H. Shamana, E. Papp-Szabo, J. Atkinson, C. Miki and J.R. Dutcher. Phytoglycogen Nanoparticles in Water: A Model Soft Colloid System, in preparation

Interactions of the Anticancer Drug Tamoxifen with Lipid Membranes

AbstractInteractions of the hydrophobic anticancer drug tamoxifen (TAM) with lipid model membranes were studied using calcein-encapsulated vesicle leakage, attenuated total reflection Fourier transform infrared (FTIR) spectroscopy, small-angle neutron scattering (SANS), atomic force microscopy (AFM) based force spectroscopy, and all-atom molecular dynamics (MD) simulations. The addition of TAM enhances membrane permeability, inducing calcein to translocate from the interior to the exterior of lipid vesicles. A large decrease in the FTIR absorption band’s magnitude was observed in the hydrocarbon chain region, suggesting suppressed bond vibrational dynamics. Bilayer thickening was determined from SANS data. Force spectroscopy measurements indicate that the lipid bilayer area compressibility modulus KA is increased by a large amount after the incorporation of TAM. MD simulations show that TAM decreases the lipid area and increases chain order parameters. Moreover, orientational and positional analyses show that TAM exhibits a highly dynamic conformation within the lipid bilayer. Our detailed experimental and computational studies of TAM interacting with model lipid membranes shed new light on membrane modulation by TAM

A calorimetric, volumetric and combined SANS and SAXS study of hybrid siloxane phosphocholine bilayers

Siloxanes are molecules used extensively in commercial, industrial, and biomedical applications. The inclusion of short siloxane chains into phospholipids results in interesting physical properties, including the ability to form low polydispersity unilamellar vesicles. As such, hybrid siloxane phosphocholines (SiPCs) have been examined as a potential platform for the delivery of therapeutic agents. Using small angle X-ray and neutron scattering, vibrating tube densitometry, and differential scanning calorimetry, we studied four hybrid SiPCs bilayers. Lipid volume measurements for the different SiPCs compared well with those previously determined for polyunsaturated PCs. Furthermore, the different SiPC\u27s membrane thicknesses increased monotonically with temperature and, for the most part, consistent with the behavior observed in unsaturated lipids such as, 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine and 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine, and the branched lipid 1,2-diphytanoyl-sn-glyerco-3-phosphocholine (DPhyPC)

Cholesterol\u27s location in lipid bilayers

It is well known that cholesterol modifies the physical properties of lipid bilayers. For example, the much studied liquid-ordered Lo phase contains rapidly diffusing lipids with their acyl chains in the all trans configuration, similar to gel phase bilayers. Moreover, the Lo phase is commonly associated with cholesterol-enriched lipid rafts, which are thought to serve as platforms for signaling proteins in the plasma membrane. Cholesterol\u27s location in lipid bilayers has been studied extensively, and it has been shown – at least in some bilayers – to align differently from its canonical upright orientation, where its hydroxyl group is in the vicinity of the lipid–water interface. In this article we review recent works describing cholesterol\u27s location in different model membrane systems with emphasis on results obtained from scattering, spectroscopic and molecular dynamics studies

\u3csup\u3e1\u3c/sup\u3eH NMR Shows Slow Phospholipid Flip-Flop in Gel and Fluid Bilayers

We measured the transbilayer diffusion of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in large unilamellar vesicles, in both the gel (Lβ′) and fluid (Lα) phases. The choline resonance of headgroup-protiated DPPC exchanged into the outer leaflet of headgroup-deuterated DPPC-d13 vesicles was monitored using 1H NMR spectroscopy, coupled with the addition of a paramagnetic shift reagent. This allowed us to distinguish between the inner and outer bilayer leaflet of DPPC, to determine the flip-flop rate as a function of temperature. Flip-flop of fluid-phase DPPC exhibited Arrhenius kinetics, from which we determined an activation energy of 122 kJ mol-1. In gel-phase DPPC vesicles, flip-flop was not observed over the course of 250 h. Our findings are in contrast to previous studies of solid-supported bilayers, where the reported DPPC translocation rates are at least several orders of magnitude faster than those in vesicles at corresponding temperatures. We reconcile these differences by proposing a defect-mediated acceleration of lipid translocation in supported bilayers, where long-lived, submicron-sized holes resulting from incomplete surface coverage are the sites of rapid transbilayer movement

Cholesterol shows preference for the interior of polyunsaturated lipid

Recent neutron scattering experiments showed a striking manifestation of the aversion between polyunsaturated fatty acid (PUFA)-containing lipids and cholesterol. Selectively deuterated cholesterol/1,2-diarachidonylphosphabdylcholine (DAPC) samples revealed that the hydroxyl of the sterol resides at the center of the bilayer. Here we use a recently parametrized coarse grain simulation model to shed light on these puzzling experimental observations. Using a simulation setup in close correspondence to the experimental conditions, we reproduce the experimental neutron scattering profiles to a large extent. The simulations allow us to analyze the behavior of cholesterol in detail; we show that the interaction of cholesterol with the PUFA chains of DAPC leads to a fast flip-flop rate for the sterol and an increased preference of the sterol for the unusual location embedded between the monolayer leaflets