Browsing by Author "Zaccai, NR"

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    Investigation on the relationship between lipid composition and structure in model membranes composed of extracted natural phospholipids
    (Elsevier B. V., 2023-01-11) Santamaria, A; Batchu, KC; Fragneto, G; Laux, V; Haertlein, M; Darwish, TA; Russell, RA; Zaccai, NR; Guzmán, E; Maestro, A
    Hypothesis Unravelling the structural diversity of cellular membranes is a paramount challenge in life sciences. In particular, lipid composition affects the membrane collective behaviour, and its interactions with other biological molecules. Experiments Here, the relationship between membrane composition and resultant structural features was investigated by surface pressure-area isotherms, Brewster angle microscopy and neutron reflectometry on in vitro membrane models of the mammalian plasma and endoplasmic-reticulum-Golgi intermediate compartment membranes in the form of Langmuir monolayers. Natural extracted yeast lipids were used because, unlike synthetic lipids, the acyl chain saturation pattern of yeast and mammalian lipids are similar. Findings The structure of the model membranes, orthogonal to the plane of the membrane, as well as their lateral packing, were found to depend strongly on their specific composition, with cholesterol having a major influence on the in-plane morphology, yielding a coexistence of liquid-order and liquid-disorder phases. © 2023 Elsevier B.V.
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    Strikingly different roles of SARS-CoV‑2 fusion peptides uncovered by neutron scattering
    (American Chemical Society (ACS), 2022-02-14) Santamaria, A; Batchu, KC; Matsarskaia, O; Prévost, SF; Russo, D; Natali, F; Seydel, T; Hoffmann, I; Laux, V; Haertlein, M; Darwish, TA; Russell, RA; Corucci, G; Fragneto, G; Maestro, A; Zaccai, NR
    Coronavirus disease-2019 (COVID-19), a potentially lethal respiratory illness caused by the coronavirus SARS-CoV-2, emerged in the end of 2019 and has since spread aggressively across the globe. A thorough understanding of the molecular mechanisms of cellular infection by coronaviruses is therefore of utmost importance. A critical stage in infection is the fusion between viral and host membranes. Here, we present a detailed investigation of the role of selected SARS-CoV-2 Spike fusion peptides, and the influence of calcium and cholesterol, in this fusion process. Structural information from specular neutron reflectometry and small angle neutron scattering, complemented by dynamics information from quasi-elastic and spin-echo neutron spectroscopy, revealed strikingly different functions encoded in the Spike fusion domain. Calcium drives the N-terminal of the Spike fusion domain to fully cross the host plasma membrane. Removing calcium, however, reorients the peptide back to the lipid leaflet closest to the virus, leading to significant changes in lipid fluidity and rigidity. In conjunction with other regions of the fusion domain, which are also positioned to bridge and dehydrate viral and host membranes, the molecular events leading to cell entry by SARS-CoV-2 are proposed. © 2022 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY-NC-ND 4.0.