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| 2. |
- Cárdenas, Marité, et al.
(författare)
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Review of structural design guiding the development of lipid nanoparticles for nucleic acid delivery
- 2023
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Ingår i: Current Opinion in Colloid and Interface Science. - : Elsevier. - 1359-0294 .- 1879-0399. ; 66
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Forskningsöversikt (refereegranskat)abstract
- Lipid nanoparticles (LNPs) are the most versatile and successful gene delivery systems, notably highlighted by their use in vaccines against COVID-19. LNPs have a well-defined core–shell structure, each region with its own distinctive compositions, suited for a wide range of in vivo delivery applications. Here, we discuss how a detailed knowledge of LNP structure can guide LNP formulation to improve the efficiency of delivery of their nucleic acid payload. Perspectives are detailed on how LNP structural design can guide more efficient nucleic acid transfection. Views on key physical characterization techniques needed for such developments are outlined including opinions on biophysical approaches both correlating structure with functionality in biological fluids and improving their ability to escape the endosome and deliver they payload.
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| 3. |
- Clifton, Luke A, et al.
(författare)
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Design and use of model membranes to study biomolecular interactions using complementary surface-sensitive techniques.
- 2020
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Ingår i: Advances in Colloid and Interface Science. - : Elsevier. - 0001-8686 .- 1873-3727. ; 277
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Tidskriftsartikel (refereegranskat)abstract
- Cellular membranes are complex structures and simplified analogues in the form of model membranes or biomembranes are used as platforms to understand fundamental properties of the membrane itself as well as interactions with various biomolecules such as drugs, peptides and proteins. Model membranes at the air-liquid and solid-liquid interfaces can be studied using a range of complementary surface-sensitive techniques to give a detailed picture of both the structure and physicochemical properties of the membrane and its resulting interactions. In this review, we will present the main planar model membranes used in the field to date with a focus on monolayers at the air-liquid interface, supported lipid bilayers at the solid-liquid interface and advanced membrane models such as tethered and floating membranes. We will then briefly present the principles as well as the main type of information on molecular interactions at model membranes accessible using a Langmuir trough, quartz crystal microbalance with dissipation monitoring, ellipsometry, atomic force microscopy, Brewster angle microscopy, Infrared spectroscopy, and neutron and X-ray reflectometry. A consistent example for following biomolecular interactions at model membranes is used across many of the techniques in terms of the well-studied antimicrobial peptide Melittin. The overall objective is to establish an understanding of the information accessible from each technique, their respective advantages and limitations, and their complementarity.
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| 4. |
- Correa M., Yubexi Y.
(författare)
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Role of lipoprotein structure and dynamics in disease development : from atherosclerosis to Covid-19
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lipoproteins play a crucial role in lipid metabolism, serving as carriers for lipids such as cholesterol and triglycerides in the bloodstream. Atherosclerosis is a complex cardiovascular disease characterized by the accumulation of cholesterol-rich plaques in arterial walls, leading to narrowed and hardened arteries. Recently, the spike protein from the SARS-CoV-2 virus, responsible for COVID-19, has been the subject of research concerning its potential impact on lipid metabolism and its association with cardiovascular disease. Understanding the interaction between lipoproteins and the spike protein influence on lipid metabolism could have implications for our knowledge of cardiovascular health.In this research, we investigated the ultrastructure of HDL from individuals with different lipid profiles as well as the interaction of mature HDL and model of nascent HDL with model membranes. Understanding these differences will help create novel rHDL particles with superior lipid-removing and CVD-treating properties. Finally, the interaction between the spike protein and HDL in model cell membranes to study potential imbalances in lipid metabolism. To achieve the different objectives, lipid deposition, exchange and removal were followed by techniques such as Neutron reflection and attenuated total reflection Fourier transformation infrared spectroscopy while, the ultrastructure was unravelled by small-angle X-ray scattering.
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| 5. |
- Correa, Yubexi, et al.
(författare)
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High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner
- 2023
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 645, s. 627-638
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Tidskriftsartikel (refereegranskat)abstract
- There is a close relationship between the SARS-CoV-2 virus and lipoproteins, in particular high-density lipoprotein (HDL). The severity of the coronavirus disease 2019 (COVID-19) is inversely correlated with HDL plasma levels. It is known that the SARS-CoV-2 spike (S) protein binds the HDL particle, probably depleting it of lipids and altering HDL function. Based on neutron reflectometry (NR) and the ability of HDL to efflux cholesterol from macrophages, we confirm these observations and further identify the preference of the S protein for specific lipids and the consequent effects on HDL function on lipid exchange ability. Moreover, the effect of the S protein on HDL function differs depending on the individuals lipid serum profile. Contrasting trends were observed for individuals presenting low triglycerides/high cholesterol serum levels (LTHC) compared to high triglycerides/high cholesterol (HTHC) or low triglycerides/low cholesterol serum levels (LTLC). Collectively, these results suggest that the S protein interacts with the HDL particle and, depending on the lipid profile of the infected individual, it impairs its function during COVID-19 infection, causing an imbalance in lipid metabolism.
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| 6. |
- Correa, Yubexi, et al.
(författare)
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Lipid exchange of apolipoprotein A-I amyloidogenic variants in reconstituted high-density lipoprotein with artificial membranes
- 2024
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Ingår i: Protein Science. - : John Wiley & Sons. - 0961-8368 .- 1469-896X. ; 33:5
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Tidskriftsartikel (refereegranskat)abstract
- High-density lipoproteins (HDLs) are responsible for removing cholesterol from arterial walls, through a process known as reverse cholesterol transport. The main protein in HDL, apolipoprotein A-I (ApoA-I), is essential to this process, and changes in its sequence significantly alter HDL structure and functions. ApoA-I amyloidogenic variants, associated with a particular hereditary degenerative disease, are particularly effective at facilitating cholesterol removal, thus protecting carriers from cardiovascular disease. Thus, it is conceivable that reconstituted HDL (rHDL) formulations containing ApoA-I proteins with functional/structural features similar to those of amyloidogenic variants hold potential as a promising therapeutic approach. Here we explored the effect of protein cargo and lipid composition on the function of rHDL containing one of the ApoA-I amyloidogenic variants G26R or L174S by Fourier transformed infrared spectroscopy and neutron reflectometry. Moreover, small-angle x-ray scattering uncovered the structural and functional differences between rHDL particles, which could help to comprehend higher cholesterol efflux activity and apparent lower phospholipid (PL) affinity. Our findings indicate distinct trends in lipid exchange (removal vs. deposition) capacities of various rHDL particles, with the rHDL containing the ApoA-I amyloidogenic variants showing a markedly lower ability to remove lipids from artificial membranes compared to the rHDL containing the native protein. This effect strongly depends on the level of PL unsaturation and on the particles' ultrastructure. The study highlights the importance of the protein cargo, along with lipid composition, in shaping rHDL structure, contributing to our understanding of lipid-protein interactions and their behavior.
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| 7. |
- Correa, Yubexi, et al.
(författare)
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SARS-CoV-2 spike protein removes lipids from model membranes and interferes with the capacity of high density lipoprotein to exchange lipids
- 2021
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 602, s. 732-739
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Tidskriftsartikel (refereegranskat)abstract
- Cholesterol has been shown to affect the extent of coronavirus binding and fusion to cellular membranes. The severity of Covid-19 infection is also known to be correlated with lipid disorders. Furthermore, the levels of both serum cholesterol and high-density lipoprotein (HDL) decrease with Covid-19 severity, with normal levels resuming once the infection has passed. Here we demonstrate that the SARS-CoV-2 spike (S) protein interferes with the function of lipoproteins, and that this is dependent on cholesterol. In particular, the ability of HDL to exchange lipids from model cellular membranes is altered when co-incubated with the spike protein. Additionally, the S protein removes lipids and cholesterol from model membranes. We propose that the S protein affects HDL function by removing lipids from it and remodelling its composition/structure.
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| 8. |
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| 9. |
- Del Giudice, Rita, et al.
(författare)
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Expanding the Toolbox for Bicelle-Forming Surfactant–Lipid Mixtures
- 2022
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 27:21, s. 7628-7628
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Tidskriftsartikel (refereegranskat)abstract
- Bicelles are disk-shaped models of cellular membranes used to study lipid–protein interactions, as well as for structural and functional studies on transmembrane proteins. One challenge for the incorporation of transmembrane proteins in bicelles is the limited range of detergent and lipid combinations available for the successful reconstitution of proteins in model membranes. This is important, as the function and stability of transmembrane proteins are very closely linked to the detergents used for their purification and to the lipids that the proteins are embedded in. Here, we expand the toolkit of lipid and detergent combinations that allow the formation of stable bicelles. We use a combination of dynamic light scattering, small-angle X-ray scattering and cryogenic electron microscopy to perform a systematic sample characterization, thus providing a set of conditions under which bicelles can be successfully formed.
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| 10. |
- Grad, Philipp
(författare)
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Effects of gangliosides and PEG-lipids on the structure, properties and interactions of lipid self-assemblies
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- When developing or utilizing lipid-based nanocarriers detailed structural characterization of the lipid self-assemblies, as well as in depth knowledge and control of their interaction with solids materials, is necessary to understand the behaviour. Disregarding one of the parameters can lead to misinterpretation of the results due to non-uniform samples or experimental artifacts caused by undesirable interactions with solid surfaces. Work included in this thesis show that gangliosides promote structural transitions of PEGylated liposomes to bilayer disks. The results suggest that the proposed ability of gangliosides to attenuate the anti-PEG immune response could be coupled to their ability to promote disk-formation.The results of this thesis further emphasize the importance of processes taking place at the solution-solid interface between self-assembled lipid particles and solid surfaces. Silica surfaces were here of particular interest, and the results showed that PEGylated lipid nanocarriers, such as liposomes and lipodisks, spontaneously attach to the material. It was further shown that an elevation of the temperature can lead to irreversible structural changes, such as the formation of supported lipid bilayers. Interestingly, the investigations revealed that defect free supported lipid bilayers (SLB) can be formed from liposomes in the gel phase. The processes at the solution-solid interface are of relevance if the solute permeability of lipid membranes are investigated with the help of liposomes in combination with spectroscopic methods. Experimental artifacts resulting from processes at the solution-cuvette interface affect the measurements and impair the reliability of the results. In order to solve this issue we explored two methods to passivated the cuvette interface, and thus prevent, or minimize, the attractive interactions between the lipid particles and the cuvette walls. In the first case a PEG-polymer and in the second a SLB was used. Both methods have their individual advantages and our findings highlight the importance of a conscious selection of the experimental procedure.
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