Daniel Topgaard

Lund University, Lund, Skåne, Sweden

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Publications (79)229.07 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A combination of NMR Chemical Shift Imaging and self-diffusion experiments is shown to give a detailed molecular picture of the events that occur when drug-loaded tablets of hydrophobically modified poly(acrylic acid) swell in water in the presence or absence of surfactant. The hydrophobic substituents on the polymer bind and trap the surfactant molecules in mixed micelles, leading to a slow effective transport of the surfactant. The transport occurs via a small fraction of individually dissolved surfactant molecules in the water domain. Due to the efficient binding of surfactant, the penetrating water is found to diffuse past the penetrating surfactant into the polymer matrix, pushing the surfactant front outwards as the matrix swells. The added surfactant has little effect on the transport of griseofulvin, because both undissolved solid drug and surfactant-solubilized drug functions as reservoirs that essentially follow the polymer as it swells. However, the added surfactant nevertheless has a strong indirect effect on the release of griseofulvin, through the effect of the surfactant on the solubility and erosion of the polymer matrix. The surfactant effectively solubilizes the hydrophobically modified polymer, making it fully miscible with water, leading to a more pronounced swelling and a slower erosion of the polymer matrix.
    The journal of physical chemistry. B. 07/2014;
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    ABSTRACT: In this work we present the first in vivo experiments employing magic angle spinning of the q-vector (qMAS) to map the microscopic anisotropy of the brain. This technique allows for the parameterization of anisotropy that is unaffected by the orientation dispersion. This means that the anisotropy is probed on a sub-voxel scale, and can potentially be useful in complex white matter geometries and gray matter, where conventional metrics such as FA are confounded by the tissue micro architecture.
    ISMRM, Milan, Italy; 05/2014
  • ISMRM, Milan, Italy; 05/2014
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    ABSTRACT: The outermost layer of the skin, the stratum corneum (SC), is a lipid-protein membrane that experiences considerable osmotic stress from a dry and cold climate. The natural moisturizing factor (NMF) comprises small and polar substances, which like osmolytes can protect living systems from osmotic stress. NMF is commonly claimed to increase the water content in the SC and thereby protect the skin from dryness. In this work we challenge this proposed mechanism, and explore the influence of NMF on the lipid and protein components in the SC. We employ natural-abundance (13)C solid-state NMR methods to investigate how the SC molecular components are influenced by urea, glycerol, pyrrolidone carboxylic acid (PCA), and urocanic acid (UCA), all of which are naturally present in the SC as NMF compounds. Experiments are performed with intact SC, isolated corneocytes and model lipids. The combination of NMR experiments provides molecularly resolved qualitative information on the dynamics of different SC lipid and protein components. We obtain completely novel molecular information on the interaction of these NMF compounds with the SC lipids and proteins. We show that urea and glycerol, which are also common ingredients in skin care products, increase the molecular mobility of both SC lipids and proteins at moderate relative humidity where the SC components are considerably more rigid in the absence of these compounds. This effect cannot be attributed to increased SC water content. PCA has no detectable effect on SC molecular mobility under the conditions investigated. It is finally shown that the more apolar compound, UCA, specifically influences the mobility of the SC lipid regions. The present results show that the NMF components act to retain the fluidity of the SC molecular components under dehydrating conditions in such a way that the SC properties remain largely unchanged as compared to more hydrated SC. These findings provide a new molecular insight into how small polar molecules in NMF and skin care products act to protect the human skin from drying.
    Soft Matter 05/2014; · 3.91 Impact Factor
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    ABSTRACT: Diffusion tensor imaging (DTI) is the method of choice for non-invasive investigations of the structure of human brain white matter (WM). The results are conventionally reported as maps of the fractional anisotropy (FA), which is a parameter related to microstructural features such as axon density, diameter, and myelination. The interpretation of FA in terms of microstructure becomes ambiguous when there is a distribution of axon orientations within the image voxel. In this paper, we propose a procedure for resolving this ambiguity by determining a new parameter, the microscopic fractional anisotropy (μFA), which corresponds to the FA without the confounding influence of orientation dispersion. In addition, we suggest a method for measuring the orientational order parameter (OP) for the anisotropic objects. The experimental protocol is capitalizing on a recently developed diffusion nuclear magnetic resonance (NMR) pulse sequence based on magic-angle spinning of the q-vector. Proof-of-principle experiments are carried out on microimaging and clinical MRI equipment using lyotropic liquid crystals and plant tissues as model materials with high μFA and low FA on account of orientation dispersion. We expect the presented method to be especially fruitful in combination with DTI and high angular resolution acquisition protocols for neuroimaging studies of gray and white matter.
    Frontiers of Physics 02/2014; 2(11). · 1.59 Impact Factor
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    ABSTRACT: The ability of lyotropic liquid crystals to form intricate structures on a range of length scales can be utilized for the synthesis of structurally complex inorganic materials, as well as in devices for controlled drug delivery. Here we employ magnetic resonance imaging (MRI) for non-invasive characterization of nano-, micro-, and millimeter scale structures in liquid crystals. The structure is mirrored in the translational and rotational motion of the water, which we assess by measuring spatially resolved self-diffusion tensors and [Formula: see text] spectra. Our approach differs from previous works in that the MRI parameters are mapped with spatial resolution in all three dimensions, thus allowing for detailed studies of liquid crystals with complex millimeter-scale morphologies that are stable on the measurement time-scale of 10 hours. The [Formula: see text] data conveys information on the nanometer-scale structure of the liquid crystalline phase, while the combination of diffusion and [Formula: see text] data permits an estimate of the orientational distribution of micrometer-scale anisotropic domains. We study lamellar phases consisting of the nonionic surfactant C10E3 in [Formula: see text]O, and follow their structural equilibration after a temperature jump and the cessation of shear. Our experimental approach may be useful for detailed characterization of liquid crystalline materials with structures on multiple length scales, as well as for studying the mechanisms of phase transitions.
    PLoS ONE 01/2014; 9(6):e98752. · 3.73 Impact Factor
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    ABSTRACT: The structure of the lamellar phase of pentaethyleneglycol mono n-dodecyl ether (C12E5) surfactant at various temperatures and molar fractions is studied by using united atom molecular dynamics simulations and nuclear magnetic resonance measurements. Namely, the simulation model is used to interpret the magnitude and temperature dependence of experimental C-H order parameter profiles in terms of molecular conformation and orientation. Our simulations suggest that the low order parameters that are generally measured in poly(ethylene oxide) surfactant bilayers are due to the presence of bilayer pores throughout the entire lamellar phase region.
    Langmuir 12/2013; · 4.38 Impact Factor
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    ABSTRACT: A new technique has been developed using NMR Chemical Shift Imaging (CSI) to monitor water penetration and molecular transport in initially dry polymer tablets that also contain small low-molecular weight compounds to be released from the tablets. Concentration profiles of components contained in the swelling tablets could be extracted via the intensities and chemical shift changes of peaks corresponding to protons of the components. The studied tablets contained hydrophobically modified poly (acrylic acid) (HMPAA) as the polymer component and griseofulvin and ethanol as hydrophobic and hydrophilic, respectively, low-molecular weight model compounds. The water solubility of HMPAA could be altered by titration with NaOH. In the pure acid form, HMPAA tablets only underwent a finite swelling until the maximum water content of the polymer-rich phase, as confirmed by independent phase studies, had been reached. By contrast, after partial neutralization with NaOH, the polyacid became fully miscible with water. The solubility of the polymer affected the water penetration, the polymer release and the releases of both ethanol and griseofulvin. The detailed NMR CSI concentration profiles obtained highlighted the clear differences in the disintegration/dissolution/release behavior for the two types of tablet and provided insights into their molecular origin. The study illustrates the potential of the NMR CSI technique to give information of importance for the development of pharmaceutical tablets and, more broadly, for the general understanding of any operation that involves the immersion and ultimate disintegration of a dry polymer matrix in a solvent.
    Langmuir 10/2013; · 4.38 Impact Factor
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    ABSTRACT: The stratum corneum (SC) is an effective permeability barrier. One strategy to increase drug delivery across skin is to increase the hydration. A detailed description of how hydration affects skin permeability requires characterization of both macroscopic and molecular properties and how they respond to hydration. We explore this issue by performing impedance experiments on excised skin membranes in the frequency range 1 Hz to 0.2 MHz under the influence of a varying gradient in water activity (aw). Hydration/dehydration induces reversible changes of membrane resistance and effective capacitance. On average, the membrane resistance is 14 times lower and the effective capacitance is 1.5 times higher when the outermost SC membrane is exposed to hydrating conditions (aw = 0.992), as compared to the case of more dehydrating conditions (aw = 0.826). Molecular insight into the hydration effects on the SC components is provided by natural-abundance (13)C polarization transfer solid-state NMR and x-ray diffraction under similar hydration conditions. Hydration has a significant effect on the dynamics of the keratin filament terminals and increases the interchain spacing of the filaments. The SC lipids are organized into lamellar structures with ∼ 12.6 nm spacing and hexagonal hydrocarbon chain packing with mainly all-trans configuration of the acyl chains, irrespective of hydration state. Subtle changes in the dynamics of the lipids due to mobilization and incorporation of cholesterol and long-chain lipid species into the fluid lipid fraction is suggested to occur upon hydration, which can explain the changes of the impedance response. The results presented here provide information that is useful in explaining the effect of hydration on skin permeability.
    Biophysical Journal 06/2013; 104(12):2639-50. · 3.67 Impact Factor
  • Diana Bernin, Daniel Topgaard
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    ABSTRACT: Heterogeneous materials, such as biological tissues, foodstuffs, and rocks, contain a range of microscopic environments where the molecular constituents often have different NMR relaxation time constants and self-diffusion coefficients. Multidimensional correlation methods have greatly improved the possibility for separating and assigning the NMR responses from distinct environments, thereby allowing for a more complete characterization of structure, dynamics, and molecular exchange in heterogeneous materials. Here, we review recent developments in experimental methodology and data analysis approaches.
    Current Opinion in Colloid & Interface Science 06/2013; 18(3):166–172. · 6.63 Impact Factor
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    ABSTRACT: Spectral editing with CP and INEPT in (13)C MAS NMR enables identification of rigid and mobile molecular segments in concentrated assemblies of surfactants, lipids, and/or proteins. In order to get stricter definitions of the terms "rigid" and "mobile", as well as resolving some ambiguities in the interpretation of CP and INEPT data, we have developed a theoretical model for calculating the CP and INEPT intensities as a function of rotational correlation time τc and C-H bond order parameter SCH, taking the effects of MAS into account. According to the model, the range of τc can at typical experimental settings (5kHz MAS, 1ms ramped CP at 80-100kHz B1 fields) be divided into four regimes: fast (τc<1ns), fast-intermediate (τc≈0.1μs), intermediate (τc≈1μs), and slow (τc>0.1ms). In the fast regime, the CP and INEPT intensities are independent of τc, but strongly dependent on |SCH|, with a cross-over from dominating INEPT to dominating CP at |SCH|>0.1. In the intermediate regime, neither CP nor INEPT yield signal on account of fast T1ρ and T2 relaxation. In both the fast-intermediate and slow regimes, there is exclusively CP signal. The theoretical predictions are tested by experiments on the glass-forming surfactant n-octyl-β-d-maltoside, for which τc can be varied continuously in the nano- to millisecond range by changing the temperature and the hydration level. The atomistic details of the surfactant dynamics are investigated with MD simulations. Based on the theoretical model, we propose a procedure for calculating CP and INEPT intensities directly from MD simulation trajectories. While MD shows that there is a continuous gradient of τc from the surfactant polar headgroup towards the methyl group at the end of the hydrocarbon chain, analysis of the experimental CP and INEPT data indicates that this gradient gets steeper with decreasing temperature and hydration level, eventually spanning four orders of magnitude at completely dry conditions.
    Journal of Magnetic Resonance 04/2013; 230:165. · 2.30 Impact Factor
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    ABSTRACT: Despite the enormous potential for pharmaceutical applications, there is still a lack of understanding of the molecular details that can contribute to increased permeability of the stratum corneum (SC). To investigate the influence of hydration and heating on the SC, we record the natural-abundance (13)C signal of SC using polarization transfer solid-state NMR methods. Resonance lines from all major SC components are assigned. Comparison of the signal intensities obtained with the INEPT and CP pulse sequences gives information on the molecular dynamics of SC components. The majority of the lipids are rigid at 32°C, and those lipids co-exist with a small pool of mobile lipids. The ratio between mobile and rigid lipids increases with hydration. An abrupt change of keratin filament dynamics occurs at RH = 80-85%, from completely rigid to a structure with rigid backbone and mobile protruding terminals. Heating has a strong effect on the lipid mobility, but only a weak influence on the keratin filaments. The results provide novel molecular insight into how the SC constituents are affected by hydration and heating, and improve the understanding of enhanced SC permeability, which is associated with elevated temperatures and SC hydration.
    PLoS ONE 01/2013; 8(4):e61889. · 3.73 Impact Factor
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    ABSTRACT: Amyloid deposits from several human diseases have been found to contain membrane lipids. Co-aggregation of lipids and amyloid proteins in amyloid aggregates, and the related extraction of lipids from cellular membranes, can influence structure and function in both the membrane and the formed amyloid deposit. Co-aggregation can therefore have important implications for the pathological consequences of amyloid formation. Still, very little is known about the mechanism behind co-aggregation and molecular structure in the formed aggregates. To address this, we study in vitro co-aggregation by incubating phospholipid model membranes with the Parkinson's disease-associated protein, α-synuclein, in monomeric form. After aggregation, we find spontaneous uptake of phospholipids from anionic model membranes into the amyloid fibrils. Phospholipid quantification, polarization transfer solid-state NMR and cryo-TEM together reveal co-aggregation of phospholipids and α-synuclein in a saturable manner with a strong dependence on lipid composition. At low lipid to protein ratios, there is a close association of phospholipids to the fibril structure, which is apparent from reduced phospholipid mobility and morphological changes in fibril bundling. At higher lipid to protein ratios, additional vesicles adsorb along the fibrils. While interactions between lipids and amyloid-protein are generally discussed within the perspective of different protein species adsorbing to and perturbing the lipid membrane, the current work reveals amyloid formation in the presence of lipids as a co-aggregation process. The interaction leads to the formation of lipid-protein co-aggregates with distinct structure, dynamics and morphology compared to assemblies formed by either lipid or protein alone.
    PLoS ONE 01/2013; 8(10):e77235. · 3.73 Impact Factor
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    ABSTRACT: The concentration of cholesterol in cell membranes affects membrane fluidity and thickness, and might regulate different processes such as the formation of lipid rafts. Since interpreting experimental data from biological membranes is rather intricate, investigations on simple models with biological relevance are necessary to understand the natural systems. We study the effect of cholesterol on the molecular structure of multi-lamellar vesicles (MLVs) composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a phospholipid ubiquitous in cell membranes, with compositions in the range 0-60 mol% cholesterol. Order parameters, |S(CH)|, are experimentally determined by using (1)H-(13)C solid-state nuclear magnetic resonance (NMR) spectroscopy with segmental detail for all parts of both the cholesterol and POPC molecules, namely the ring system and alkyl chain of the sterol, as well as the glycerol backbone, choline headgroup and the sn-1 and sn-2 acyl chains of POPC. With increasing cholesterol concentration the acyl chains gradually adopt a more extended conformation while the orientation and dynamics of the polar groups are rather unaffected. Additionally, we perform classical molecular dynamics simulations on virtual bilayers mimicking the POPC-cholesterol MLVs investigated by NMR. Good agreement between experiments and simulations is found for the cholesterol alignment in the bilayer and for the |S(CH)| profiles of acyl chains below 15 mol% cholesterol. Deviations occur for the choline headgroup and glycerol backbone parts of POPC, as well as for the phospholipid and cholesterol alkyl chains at higher cholesterol concentrations. The unprecedented detail of the NMR data enables a more complete comparison between simulations and experiments on POPC-cholesterol bilayers and may aid in developing more realistic model descriptions of biological membranes.
    Physical Chemistry Chemical Physics 12/2012; · 3.83 Impact Factor
  • Stefanie Eriksson, Samo Lasic, Daniel Topgaard
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    ABSTRACT: When PGSE NMR is applied to water in microheterogeneous materials such as liquid crystals, foodstuffs, porous rocks, and biological tissues, the signal attenuation is often multi-exponential, indicating the presence of pores having a range of sizes or anisotropic domains having a spread of orientations. Here we modify the standard PGSE experiment by introducing low-amplitude harmonically modulated gradients, which effectively make the q-vector perform magic-angle spinning (MAS) about an axis fixed in the laboratory frame. With this new technique, denoted q-MAS PGSE, the signal attenuation depends on the isotropic average of the local diffusion tensor. The capability of q-MAS PGSE to distinguish between pore size and domain orientation dispersion is demonstrated by experiments on a yeast cell suspension and a polydomain anisotropic liquid crystal. In the latter case, the broad distribution of apparent diffusivities observed with PGSE is narrowed to its isotropic average with q-MAS PGSE in a manner that is analogous to the narrowing of chemical shift anisotropy powder patterns using magic-angle sample spinning in solid-state NMR. The new q-MAS PGSE technique could be useful for resolving size/orientation ambiguities in the interpretation of PGSE data from, e.g., water confined within the axons of human brain tissue.
    Journal of Magnetic Resonance 11/2012; 226C:13-18. · 2.30 Impact Factor
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    ABSTRACT: We present the first in vivo application of the filter-exchange imaging protocol for diffusion MRI. The protocol allows noninvasive mapping of the rate of water exchange between microenvironments with different self-diffusivities, such as the intracellular and extracellular spaces in tissue. Since diffusional water exchange across the cell membrane is a fundamental process in human physiology and pathophysiology, clinically feasible and noninvasive imaging of the water exchange rate would offer new means to diagnose disease and monitor treatment response in conditions such as cancer and edema. The in vivo use of filter-exchange imaging was demonstrated by studying the brain of five healthy volunteers and one intracranial tumor (meningioma). Apparent exchange rates in white matter range from 0.8 ± 0.08 s(-1) in the internal capsule, to 1.6 ± 0.11 s(-1) for frontal white matter, indicating that low values are associated with high myelination. Solid tumor displayed values of up to 2.9 ± 0.8 s(-1) . In white matter, the apparent exchange rate values suggest intra-axonal exchange times in the order of seconds, confirming the slow exchange assumption in the analysis of diffusion MRI data. We propose that filter-exchange imaging could be used clinically to map the water exchange rate in pathologies. Filter-exchange imaging may also be valuable for evaluating novel therapies targeting the function of aquaporins. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 07/2012; · 3.27 Impact Factor
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    ABSTRACT: Self-diffusion in polymer solutions studied with pulsed-field gradient nuclear magnetic resonance (PFG NMR) is typically based either on a single self-diffusion coefficient, or a log-normal distribution of self-diffusion coefficients, or in some cases mixtures of these. Experimental data on polyethylene glycol (PEG) solutions and simulations were used to compare a model based on a gamma distribution of self-diffusion coefficients to more established models such as the single exponential, the stretched exponential, and the log-normal distribution model with regard to performance and consistency. Even though the gamma distribution is very similar to the log-normal distribution, its NMR signal attenuation can be written in a closed form and therefore opens up for increased computational speed. Estimates of the mean self-diffusion coefficient, the spread, and the polydispersity index that were obtained using the gamma model were in excellent agreement with estimates obtained using the log-normal model. Furthermore, we demonstrate that the gamma distribution is by far superior to the log-normal, and comparable to the two other models, in terms of computational speed. This effect is particularly striking for multi-component signal attenuation. Additionally, the gamma distribution as well as the log-normal distribution incorporates explicitly a physically plausible model for polydispersity and spread, in contrast to the single exponential and the stretched exponential. Therefore, the gamma distribution model should be preferred in many experimental situations.
    Journal of Magnetic Resonance 07/2012; 222:105-11. · 2.30 Impact Factor
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    ABSTRACT: The phase diagram of the redox active ionic liquid 1-methyl-3-propylimidazolium iodide (PMII) is examined as a function of temperature and iodine concentration. Beyond a threshold concentration of 3.9 M, the formation of higher polyiodides give rise to a viscoelastic phase upon cooling. Despite of the very high viscosity of such polyiodide-containing PMII melts a strikingly high conductivity is maintained through Grotthuss-type bond exchange and ionic conduction.
    Advanced Materials 01/2012; 24(6):781-4. · 14.83 Impact Factor
  • Soft Matter 01/2012; 8:1482. · 3.91 Impact Factor
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    ABSTRACT: A compression cell designed to fit inside an NMR spectrometer was used to investigate (i) the in situ dynamic strain response and structural changes of the internal pore network, and (ii) the diffusion and flow of interstitial water, in full thickness cartilage samples as they were mechanically deformed under a constant compressive load (pressure) and then allowed to recover (swell again) when the load was removed. Selective enzymatic digestion of the collagen fibril network and the glycopolysaccharide hyaluronic acid (HA) was performed to mimic some of the structural and compositional changes associated with osteoarthritis. Digestion of collagen gave rise to mechanical ‘dynamic softening’ and—perhaps more importantly—nearly complete loss in the ability to recover through swelling, both effects due to the disruption of the hierarchical structure and fibril interconnectivity in the collagen network which adversely affects its ability to deform reversibly and to properly regulate the pressurization and resulting rate and direction of interstitial fluid flow. In contrast, digestion of HA inside the collagen pore network caused the cartilage to ‘dynamically stiffen’ which is attributed to the decrease in the osmotic (entropic) pressure of the digested HA molecules confined in the cartilage pores that causes the network to contract and thereby become less permeable to flow. These digestion-induced changes in cartilage's properties reveal a complex relationship between the molecular weight and concentration of the HA in the interstitial fluid, and the structure and properties of the collagen fibril pore network, and provide new insights into how changes in either could influence the onset and progression of osteoarthritis.
    Soft Matter 01/2012; 8:9906. · 3.91 Impact Factor

Publication Stats

429 Citations
229.07 Total Impact Points


  • 2002–2014
    • Lund University
      • • Department of Physical Chemistry
      • • Department of Medical Radiation Physics
      Lund, Skåne, Sweden
  • 2010
    • University of Oslo
      • Department of Chemistry
      Oslo, Oslo, Norway
  • 2008
    • University of California, Santa Barbara
      Santa Barbara, California, United States
  • 2004–2006
    • University of California, Berkeley
      • • Department of Materials Science and Engineering
      • • Department of Chemistry
      Berkeley, MO, United States
    • KTH Royal Institute of Technology
      • Division of Applied Physical Chemistry
      Stockholm, Stockholm, Sweden