Tag Archive for: AWS X4 000041 A

Publication on AWSensors technology

Variant-Specific Interactions at the Plasma Membrane: Heparan Sulfate’s Impact on SARS-CoV-2 Binding Kinetics

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Authors: Dario Valter Conca, Fouzia Bano, Małgorzata Graul, Julius von Wirén, Lauriane Scherrer, Hudson Pace, Himanshu Sharma, Justas Svirelis, Konrad Thorsteinsson, Andreas Dahlin, and Marta Bally

Journal: Analytical Chemistry

Abstract: The spread of SARS-CoV-2 led to the emergence of several variants of concern (VOCs). The spike glycoprotein, responsible for engaging the viral receptor, exhibits the highest density of mutations, suggesting an ongoing evolution to optimize viral entry. This study characterizes the bond formed by virion mimics carrying the SARS-CoV-2 spike protein and the plasma membrane of host cells in the early stages of virus entry. Contrary to the traditional analysis of isolated ligand-receptor pairs, we utilized well-defined biomimetic models and biochemical and biophysical techniques to characterize the multivalent interaction of VOCs with the complex cell membrane. We observed an overall increase in the binding affinity for newer VOCs. By progressively reducing the system complexity, we identify heparan sulfate (HS) as a main driver of this variation, with a 10-fold increase in affinity for Omicron BA.1 over that of the original strain. These results demonstrate the essential role of coreceptors, particularly HS, in the modulation of SARS-CoV-2 infection and highlight the importance of multiscale biophysical and biochemical assays that account for membrane complexity to fully characterize and understand the role of molecular components and their synergy in viral attachment and entry.

The full article can be accessed here.

Publication on AWSensors technology

Lipid packing frustration in the outer leaflet of the plasma membrane prevents scission of caveolae

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Authors: Elin Larsson, Aleksei Kabedev, Hudson Pace, Jakob Lindwall, Fouzia Bano, Robert G Parton, Christel A. S. Bergstrom, Ingela Parmryd, Marta Bally, Richard Lundmark

Journal: bioRxiv

Abstract: Lipid packing is a fundamental characteristic of bilayer membranes. It affects all membrane-associated processes ranging from curvature generation to membrane fission. Yet, we lack detailed, mechanistic understanding of how lipid packing directly affects these processes in cellular membranes. Here, we address this by focusing on caveolae, small Ω-shaped invaginations of the plasma membrane which serve as key regulators of cellular lipid sorting and mechano-responses. In addition to caveolae coat proteins, the lipid membrane is a core component of caveolae that critically impacts both the biogenesis, morphology and stability of such membrane invaginations. We show that the small compound Dyngo-4a inserts into the membrane, resulting in a dramatic dynamin-independent inhibition of caveola scission. Analysis of model membranes in combination with molecular dynamics simulations revealed that a substantial amount of Dyngo-4a was inserted and positioned at the level of cholesterol in the bilayer. Dyngo-4a-treatment resulted in decreased lipid packing in the outer leaflet of the plasma membrane preventing scission without affecting caveola morphology, caveolae- associated proteins, or the overall membrane stiffness. Artificially increasing plasma membrane cholesterol levels was found to counteract the block in caveola scission caused by Dyngo-4a-mediated lipid packing frustration. Therefore, we propose that the packing of cholesterol in the outer leaflet of the plasma membrane critically controls the confinement of caveolae to the plasma membrane.

The full article can be accessed here.

Publication on AWSensors technology

Kinetic selectivity in metal-organic framework chemical sensors

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Authors: Aleksander Matavž, Margot F. K. Verstreken, Leen Boullart, Max L. Tietze, Masaya Sugihara, Lars Heinke, and Rob Ameloot

Journal: ChemRxiv

Abstract: Selective detection of specific volatile organic compounds (VOCs) is crucial for health, safety, and environmental applications, but current sensors suffer from poor selectivity and struggle to measure specific VOCs in the presence of interfering compounds and water vapor. To address this issue, we introduce the kinetic selectivity achievable in nanoporous crystals, specifically metal-organic frameworks (MOFs), into the domain of chemical sensors. In well-selected MOFs, similar molecules can have diffusivities that differ by orders of magnitude. Measuring these diffusivity values is challenging since conventional methods based on rapid changes in atmosphere composition cannot be used in a sensing context. A novel temperature perturbation method was developed for thin-film capacitive sensors with a MOF dielectric layer to enable diffusivity measurements in a fixed atmosphere. Our approach enabled a single sensor to differentiate and quantify VOCs at ppm concentrations, even in mixtures containing high water vapor concentrations, outperforming a state-of-the-art ten-element sensor array.

The full article can be accessed here.

Publication on AWSensors technology

Matrix Metalloproteinase-9 Mediates Endothelial Glycocalyx Degradation and Correlates with Severity of Hemorrhagic Fever with Renal Syndrome

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Authors: Chloé Jacquet. Rasmus Gustafsson, Ankit Kumar Patel, Magnus Hansson, Gregory Rankin, Fouzia Bano, Julia Wigren Byström, Anders Blomberg, Johan Rasmuson, Simon Satchell, Therese Thunberg, Clas Ahlm, Marta Bally, Anne-Marie Fors Connolly

Journal: medRxiv Preprint

Abstract: Hemorrhagic fever with renal syndrome (HFRS) caused by Puumala virus (PUUV) leads to vascular dysfunction contributing to acute kidney injury and pulmonary complications. The endothelial glycocalyx (eGLX) is crucial for vascular integrity, and its degradation may exacerbate disease severity. In this study, we examined the association between eGLX degradation and renal and pulmonary dysfunction in 44 patients with laboratory-confirmed PUUV infection. We measured plasma levels of eGLX degradation markers—syndecan-1, heparan sulfate, soluble thrombomodulin, and albumin— and found that these correlated with severe acute kidney injury and the need for oxygen therapy. In vitro experiments showed that matrix metalloproteinase-9 (MMP-9) and heparanase can degrade eGLX components, but albumin at physiological concentrations can mitigate this degradation and protect endothelial barrier function. These findings indicate that eGLX degradation contributes to HFRS pathogenesis and suggest that targeting the eGLX could be a therapeutic strategy to improve patient outcomes.

The full article can be accessed here.