| 1. |
- Brunzell, Ellen, et al.
(author)
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Investigation of supramolecular structures in various aqueous solutions of an amyloid forming peptide using small-angle X-ray scattering
- 2024
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In: Soft Matter. - : Royal Society of Chemistry. - 1744-683X .- 1744-6848. ; 20:10, s. 2272-2279
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Journal article (peer-reviewed)abstract
- Aggregation of peptide molecules into amyloid fibrils is a characteristic feature of several degenerative diseases. However, the details behind amyloid-formation, and other self-assembled peptide aggregates, remain poorly understood. In this study, we have used small-angle X-ray scattering (SAXS), static and dynamic light scattering (SLS and DLS) as well as cryogenic transmission electron microscopy (cryo-TEM) to determine the structural geometry of self-assembled peptide aggregates in various dilute aqueous solutions. Pramlintide was used as a model peptide to assess the aggregation behaviour of an amyloid-forming peptide. The effects of adding sodium chloride (NaCl), sodium thiocyanate (NaSCN), and sodium fluoride (NaF) and the co-solvent dimethyl sulfoxide (DMSO) on the aggregation behaviour were studied. Our scattering data analysis demonstrates that small oligomeric fibrils aggregate to form networks of supramolecular assemblies with fractal dimensions. The choice of anion in small amounts of added salt has a significant impact on the size of the fibrils as well as on the fractal dimensions of supramolecular clusters. In DMSO the fractal dimension decreased with increasing DMSO concentration, indicating the formation of a less compact structure of the supramolecular assemblies. The peptide pramlintide forms oligomeric species in solution, which make up a supramolecular network characterised by fractal dimensions. The fractal dimension of the network depends on solvent additive.
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| 2. |
- Forooqi Motlaq, Vahid, et al.
(author)
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Investigation of the enhanced ability of bile salt surfactants to solubilize phospholipid bilayers and form mixed micelles.
- 2021
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In: Soft Matter. - : Royal Society of Chemistry. - 1744-683X .- 1744-6848. ; 17:33, s. 7769-7780
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Journal article (peer-reviewed)abstract
- The self-assembly in mixtures of the anionic bile salt surfactant sodium deoxycholate (NaDC) and the zwitterionic phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) in physiological saline solution has been investigated using light scattering, small-angle X-ray scattering and cryo-transmission electron microscopy. Rather small tri-axial ellipsoidal NaDC-DMPC mixed micelles form at a high content of bile salt in the mixture, which increase in size as an increasing amount of DMPC is incorporated into the micelles. Eventually, the micelles begin to grow substantially in length to form long wormlike micelles. At higher mole fractions of DMPC, the samples become turbid and cryo-TEM measurements reveal the existence of large perforated vesicles (stomatosomes), coexisting with geometrically open disks. To our knowledge, stomatosomes have not been observed before for any bile salt-phospholipid system. Mixed micelles are found to be the sole aggregate structure in a very wide regime of bile salt-phospholipid compositions, i.e. up to about 77 mol% phospholipid in the micelles. This is much higher than the corresponding value of 25 mol% observed for the conventional surfactant hexadecyltrimethylammonium bromide (CTAB) mixed with DMPC in the same solvent. The enhanced ability of bile salt surfactants to solubilize phospholipid bilayers and form mixed micelles is rationalized using bending elasticity theory. From our theoretical analysis, we are able to conclude that amphiphilic molecules rank in the following order of increasing spontaneous curvature: phospholipids < conventional surfactants < bile salts. The bending rigidity of the different amphiphilic molecules increases according to the following sequence: bile salts < conventional surfactants < phospholipids.
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| 3. |
- Forooqi Motlaq, Vahid, et al.
(author)
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Spontaneous Formation of Ultrasmall Unilamellar Vesicles in Mixtures of an Amphiphilic Drug and a Phospholipid
- 2023
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In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 39:32, s. 11337-11344
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Journal article (peer-reviewed)abstract
- We have observed ultrasmall unilamellar vesicles, withdiametersof less than 20 nm, in mixtures of the tricyclic antidepressant drugamitriptyline hydrochloride (AMT) and the unsaturated zwitterionicphospholipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) in physiologicalsaline solution. The size and shape of spontaneously formed self-assembledaggregates have been characterized using complementary techniques,i.e., small-angle neutron and X-ray scattering (SANS and SAXS) andcryo-transmission electron microscopy (cryo-TEM). We observe rodlikemixed micelles in more concentrated samples that grow considerablyin length upon dilution, and a transition from micelles to vesiclesis observed as the concentration approaches the critical micelle concentrationof AMT. Unlike the micelles, the spontaneously formed vesicles decreasein size with each step of dilution, and ultrasmall unilamellar vesicles,with diameters as small as about 15 nm, were observed at the lowestconcentrations. The spontaneously formed ultrasmall unilamellar vesiclesmaintain their size for as long we have investigated them (i.e., severalmonths). To the best of our knowledge, such small vesicles have neverbefore been reported to form spontaneously in a biocompatible phospholipid-basedsystem. Most interestingly, the size of the vesicles was observedto be strongly dependent on the chemical structure of the phospholipid,and in mixtures of AMT and the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine(DMPC), the vesicles were observed to be considerably larger in size.The self-assembly behavior in the phospholipid-drug surfactantsystem in many ways resembles the formation of equilibrium micellesand vesicles in mixed anionic/cationic surfactant systems.
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