| 1. |
- Buchanan, Claire, et al.
(author)
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C-amidation of substituted β 3oligoamides yields novel supramolecular assembly motif
- 2022
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In: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 33:2
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Journal article (peer-reviewed)abstract
- N-acylated substituted β 3 oligoamides are known to form unique supramolecular nanorods based on a 3-point hydrogen bond self-assembly motif. This motif is an intermolecular extension of the hydrogen bonding network that stabilizes the 14-helix secondary structure unique to β 3 oligoamides. Acetylation of the N-terminus of the molecule provides the necessary third hydrogen bond pair of the motif. Here, the possibility of introducing the third hydrogen bond pair via amidation of the C terminus is investigated. While similar in purpose, this modification introduces a chemically distinct new self-assembly motif, also removing the bulky carboxyl group that does not fold into the 14 helix positioning instead as a side chain. Three substituted β 3 oligoamide variants with the base sequence LIA (where the letters denote β 3 residues with side chains analogous to α amino acids) were compared: N-acylated Ac-β 3[LIA] as a reference, C-amidated β 3[LIA]-CONH2, and β 3[LIA] with free unmodified N and C termini as a negative control. The three variants were dissolved in water to promote self-assembly. The self-assembly was characterised using mid- and far-infrared spectroscopy, small angle x-ray scattering (SAXS) and atomic force microscopy (AFM). IR measurements confirmed that all three samples were in a similar conformation, consistent with pseudo 14-helical secondary structures. Far-infrared spectroscopy measurements of β 3[LIA]-CONH2 showed distinct peaks consistent with highly organised skeletal modes, i.e. regular supramolecular assembly, that was largely absent from the other two oligoamides. Modelling of SAXS data is consistent with elliptical cylinder structures resulting from nanorod bundling for both β 3[LIA]-CONH2 and Ac-β 3[LIA], but not in the unmodified sample. Consistently, AFM imaging showed large nanorod bundling structures in β 3[LIA]-CONH2, varied bundling structures in Ac-β 3[LIA], and only aggregation in β 3[LIA]. Amidation showed much more organised and robust assembly compared to acetylation, providing a new, easy to synthesize self-assembly motif for helical nanorod assembly that is similar but distinct to N-acylation
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| 2. |
- Buchanan, Claire, et al.
(author)
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Comprehensive multidimensional study of the self-assembly properties of a three residue substituted beta(3) oligoamide
- 2021
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In: Pure and Applied Chemistry. - : Walter de Gruyter. - 0033-4545 .- 1365-3075. ; 93:11, s. 1327-1341
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Journal article (peer-reviewed)abstract
- Substituted (beta(3) oligoamides form a unique self-assembling system where each monomer folds into a helix containing approximately three (beta(3) amino acids per turn, yielding a geometrically well-defined cylindrical building block that, when N-acylated, is able to self-assemble head-to-tail into nanorods that can reach several 100 mu m length. It was shown in previous works that self-assembly can be achieved with a three residue long oligoamide as well that lacks any intramolecular H-bonds, yet it crystallizes in a helix-like conformation. The self-assembly properties of these small oligoamides are however elusive, suggesting a more complex system than the self-assembly of the H-bond stabilized helical monomers. Here we focus on the self-assembly behaviour of a three residue oligoamide, Ac-beta(3)[LIA] where the letters denote the side chain of the analogous a amino acid. Ac-beta(3)[LIA] can yield highly inhomogeneous suspensions in water with a broad range of large fibrous structures that seem to be very stable, yet occasionally fibre growth is only observed upon heating. The small size of the monomer suggests a highly dynamic equilibrium yet all previous attempts failed to clearly identify low molecular weight species. Therefore a special methodology was employed in this study to characterize the suspensions at different size ranges: SANS that is optimal to measure the small oligomers and cross sectional diameter of the assemblies, DLS that is sensitive to the large populations and therefore the length of the superstructures, and NMR that is sensitive to monomeric and small oligomeric form, in conjunction with IR spectroscopy to probe the folding and AFM to image the morphology of the assemblies. Temperature ramping was used to perturb the system to probe the dynamicity of the self-assembly. It was found that the anomalous self-assembly behaviour of Ac-beta(3)[LIA] is caused by its two stable conformations, a helix-building "horseshoe" fold and a linear conformer. The latter is exclusively found in monomeric form in solution whereas the horseshoe fold is stable in solid phase and in fibrous assemblies. Small oligomers were absent. Thus the self assembly of Ac-beta(3)[LIA] is arrested by the activation energy need of the conformation change; fibre growth might be triggered by conditions that allow increased conformational freedom of the monomers. This observation may be used to develop strategies for controlled switchable self-assembly.
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| 3. |
- Buchanan, Claire, et al.
(author)
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Coordination crosslinking of helical substituted oligoamide nanorods with Cu(II)
- 2020
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In: Supramolecular Chemistry. - : Informa UK Limited. - 1061-0278 .- 1029-0478. ; 32:3, s. 222-232
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Journal article (peer-reviewed)abstract
- Substituted oligoamides are short sequences of unnatural amino acids. Oligoamides made entirely of β3 amino acids yield helical monomers that, if N-acylated, assemble into nanorod structures via a supramolecular assembly motif. In this work, coordination crosslinking was used to create complex nanomaterials from oligoamides WKLWEL (KE) and WELWEL (EE) (the letters denote the analogous α-amino acids). Upon Cu(II) addition, atomic force microscopy and small angle neutron scattering revealed morphologic changes specific to KE but absent in EE. Vibration spectroscopy measurements revealed that Cu(II) can coordinate to the amine moieties of the side chains, without direct effect on the backbone amides. While coordination in excess solvent lead to regular nanostructures, fast drying of the sample yielded oligoamide templated crystallization of CuCl2. The metal coordination crosslinking of supramolecular assemblies as reported here is the first realization of a metallosupramolecular framework structure.
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| 4. |
- Cao, Cheng, et al.
(author)
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Drug-Directed Morphology Changes in Polymerization-Induced Self-Assembly (PISA) Influence the Biological Behavior of Nanoparticles
- 2020
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In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 12:27, s. 30221-30233
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Journal article (peer-reviewed)abstract
- The effect of the hydrophobic block length on the morphologies of polymerization-induced self-assembled (PISA) nanoparticles is well understood. However, the influence of drug loading on the phase morphology of the nanoparticles during the PISA process, and the resulting biological function of PISA nanoparticles, has barely been investigated. In this work, we show that the addition of a drug, curcumin, during the PISA process shifts the phase diagram toward different morphologies. The PISA system was based on hydrophilic poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC), which was chain extended with hydrophobic methyl methacrylate (MMA) in various concentrations of curcumin. According to transmission electron microscopy, the presence of curcumin led to the transition of, for example, worms to polymersome and micelles to worms analysis. To understand the interaction between polymer particles and drug, small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS), and fluorescence lifetime measurements were carried out. These measurements show that curcumin is predominantly located in the core in the case of micelles and worms while it is found in the shell of polymersomes. The change in morphology influences the cellular uptake by MCF-7 cells and the movement of the particles in multicellular cancer spheroids (3D model). With the increasing amount of drug, the cellular uptake of micelles and worms was enhanced with the increasing grafting density of MPC chains, which contrasts the decreasing cellular uptake in the higher drug-loaded polymersomes due to the lower shell hydration.
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| 5. |
- Cao, Cheng, et al.
(author)
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The Protein Corona Leads to Deformation of Spherical Micelles
- 2021
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In: Angewandte Chemie International Edition. - : John Wiley & Sons. - 1433-7851 .- 1521-3773. ; 60:18, s. 10342-10349
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Journal article (peer-reviewed)abstract
- The formation of a non-specific protein corona around nanoparticles (NPs) has been identified as one of the culprits for failed nanomedicine. The amount and type of adsorbed protein from the blood plasma are known to determine the fate of NPs and the accessibility of targeting ligands. Herein, we show that the adsorbed protein may not only enlarge the NPs and change their surface properties but also, in the case of soft NPs such as polymer micelles, lead to deformation. Poly(1-O-methacryloyl -beta-D-fructopyranose)-b-poly(methylmethacrylate) (P(1-O-MAFru)-b-PMMA) block co-polymers were self-assembled into NPs with a spherical core-shell morphology as determined by small angle neutron scattering (SANS). Upon incubation with albumin, TEM, SANS, and small angle X-ray scattering (SAXS) revealed the adsorption of albumin and deformation of the NPs with a spheroid geometry. Removal of the protein led to the reversal of the morphology back to the spherical core-shell structure. Structural studies and cell studies of uptake of the NPs imply that the observed deformation may influence blood circulation time and cell uptake.
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| 6. |
- Conn, Charlotte E, et al.
(author)
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Membrane Protein Structures in Lipid Bilayers; Small-Angle Neutron Scattering With Contrast-Matched Bicontinuous Cubic Phases
- 2020
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In: Frontiers in chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 8
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Journal article (peer-reviewed)abstract
- . Deuterated vesicles can be used to obtain the radius of gyration of membrane proteins, but protein-protein interference effects within the vesicles severely limits this method such that the protein structure cannot be modeled. We show herein that different membrane protein conformations can be distinguished within the lipid bilayer of the bicontinuous cubic phase using contrast-matching. Time-resolved studies performed using SANS illustrate the complex phase behavior in lyotropic liquid crystalline systems and emphasize the importance of this development. We believe that studying membrane protein structures and phase behavior in contrast-matched lipid bilayers will advance both biological and pharmaceutical applications of membrane-associated proteins, biosensors and food science.
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| 7. |
- Garvey, Christopher J., et al.
(author)
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Molecular-Scale Understanding of the Embrittlement in Polyethylene Ocean Debris
- 2020
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 54:18, s. 11173-11181
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Journal article (peer-reviewed)abstract
- The fate of plastic waste is a pressing issue since it forms a visible and long-lived reminder of the environmental impact of consumer habits. In this study, we examine the structural changes in the lamellar arrangements of semicrystalline polyethylene (PE) packaging waste with the aim of understanding the physical mechanisms of embrittlement in PE exposed to the marine environment. PE microplastics and macroplastics from identifiable PE packaging were collected in the Atlantic Ocean and compared to new PE boxes. Several experimental techniques interrogate the effects of environmental exposure on their bulk and surface properties. Size exclusion chromatography determines the molecular weight distribution of the PE polymer chains and differential scanning calorimetry gives the crystallinity. Small- and wide-angle X-ray scattering examines the packing of PE chains into semicrystalline lamellae. Longitudinal acoustic mode Raman spectroscopy provides a complementary measurement of the length of PE polymer chains extending through the crystalline lamellar domains. While there is a high degree of uncertainty in the time scale for the changes, the overall picture at the molecular scale is that although PE becomes more crystalline with environmental exposure, the lamellar order present in new packing boxes is disrupted by the weathering process. This process has important implications for embrittlement and subsequent degradation.
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| 8. |
- Jacobs, Susan S., et al.
(author)
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Home oxygen therapy for adults with chronic lung disease an official american thoracic society clinical practice guideline
- 2020
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In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 202:10, s. 121-141
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Journal article (peer-reviewed)abstract
- Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Methods: The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquidoxygen use in patients who are mobile outside the home and require .3 L/min of continuous-flow oxygen during exertion (very-lowquality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (bestpractice statement). Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.
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| 9. |
- Jakubauskas, Dainius, et al.
(author)
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Ultrastructural modeling of small angle scattering from photosynthetic membranes
- 2019
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Journal article (peer-reviewed)abstract
- The last decade has seen a range of studies using non-invasive neutron and X-ray techniques to probe the ultrastructure of a variety of photosynthetic membrane systems. A common denominator in this work is the lack of an explicitly formulated underlying structural model, ultimately leading to ambiguity in the data interpretation. Here we formulate and implement a full mathematical model of the scattering from a stacked double bilayer membrane system taking instrumental resolution and polydispersity into account. We validate our model by direct simulation of scattering patterns from 3D structural models. Most importantly, we demonstrate that the full scattering curves from three structurally typical cyanobacterial thylakoid membrane systems measured in vivo can all be described within this framework. The model provides realistic estimates of key structural parameters in the thylakoid membrane, in particular the overall stacking distance and how this is divided between membranes, lumen and cytoplasmic liquid. Finally, from fitted scattering length densities it becomes clear that the protein content in the inner lumen has to be lower than in the outer cytoplasmic liquid and we extract the first quantitative measure of the luminal protein content in a living cyanobacteria.
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| 10. |
- Jarrett, K. J., et al.
(author)
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The spatial modulation of microfibril angle in the woody tissue of maturing tree stems studied with synchrotron radiation
- 2020
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In: Australian Journal of Botany. - : CSIRO Publishing. - 0067-1924 .- 1444-9862. ; 68:4, s. 267-274
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Journal article (peer-reviewed)abstract
- Spatial variations in the microfibril angle (MFA) of cellulose are mapped on individual radial sections of wood from the maturing stems of Australian tree species (Acacia floribunda, Acacia suaveolens, Acacia doratoxylon, Acacia havilandiorum, Brachychiton populneus and Bertya cunninghamii) from different rainfall and soil nutrient availabilities using synchrotron wide angle X-ray scattering. For the three species with the smallest radial variation there is a clear linear relationship between the MFA with Young's modulus and wood density with data published previously for these samples. The other three samples show a large radially symmetric variation in MFA across the radial section either having a continuous change from large MFA in the stem's centre to small value close to the bark or the reverse, small MFA at the centre to larger values close to the bark. For these samples, a strong linear correlation between the Young's modulus and density and the MFA is not apparent. We conclude that spatially localised measurements of MFA provide an important insight in the adaptation of wood tissue to environmental conditions.
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