How stereochemistry of lipid components can affect lipid organization and the route of liposome internalization into cells

Borocci, Stefano; Bozzuto, Giuseppina; Bombelli, Cecilia; Ceccacci, Francesca; Formisano, Giuseppe; Stringaro, Annarita; Molinari, Agnese; Mancini, Giovanna

doi:10.1039/d1nr02175c

Cited by 9 publications

(2 citation statements)

References 83 publications

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“…Changes in the stereochemistry of lipids can affect their physicochemical properties. − Furthermore, the chirality of peptides can affect their interactions with chiral lipids, and cholesterol chirality can affect membrane protein function . Previous experiment reveals that vesicles composed of 1-palmitoyl-2-elaidoyl- sn -glycero-3-phosphocholine (Δ9- trans POPC) are less susceptible to leakage than POPC vesicles .…”

Section: Resultsmentioning

confidence: 99%

Asynchronous Reciprocal Coupling of Martini 2.2 Coarse-Grained and CHARMM36 All-Atom Simulations in an Automated Multiscale Framework

López

Zhang

Aydin

et al. 2022

J. Chem. Theory Comput.

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The appeal of multiscale modeling approaches is predicated on the promise of combinatorial synergy. However, this promise can only be realized when distinct scales are combined with reciprocal consistency. Here, we consider multiscale molecular dynamics (MD) simulations that combine the accuracy and macromolecular flexibility accessible to fixed-charge all-atom (AA) representations with the sampling speed accessible to reductive, coarse-grained (CG) representations. AA-to-CG conversions are relatively straightforward because deterministic routines with unique outcomes are achievable. Conversely, CG-to-AA conversions have many solutions due to a surge in the number of degrees of freedom. While automated tools for biomolecular CG-to-AA transformation exist, we find that one popular option, called Backward, is prone to stochastic failure and the AA models that it does generate frequently have compromised protein structure and incorrect stereochemistry. Although these shortcomings can likely be circumvented by human intervention in isolated instances, automated multiscale coupling requires reliable and robust scale conversion. Here, we detail an extension to Multiscale Machine-learned Modeling Infrastructure (MuMMI), including an improved CG-to-AA conversion tool called sinceCG. This tool is reliable (∼98% weakly correlated repeat success rate), automatable (no unrecoverable hangs), and yields AA models that generally preserve protein secondary structure and maintain correct stereochemistry. We describe how the MuMMI framework identifies CG system configurations of interest, converts them to AA representations, and simulates them at the AA scale while on-the-fly analyses provide feedback to update CG parameters. Application to systems containing the peripheral membrane protein RAS and proximal components of RAF kinase on complex eight-component lipid bilayers with ∼1.5 million atoms is discussed in the context of MuMMI.

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Section: Resultsmentioning

confidence: 99%

Asynchronous Reciprocal Coupling of Martini 2.2 Coarse-Grained and CHARMM36 All-Atom Simulations in an Automated Multiscale Framework

López

Zhang

Aydin

et al. 2022

J. Chem. Theory Comput.

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“…In the light of this, for the first time in this study, the ability of L. angustifolia extract-loaded hyalurosomes to protect skin fibroblasts from oxidative stress was confirmed by in vitro studies. The protective effect was ensured by the loading of the extract in hyalurosomes, which can interact, to a better extent than the extract in dispersion, with the cell membrane facilitating the phytochemical internalization in the cytoplasm, where they can terminate free radical chain reactions, capture free radicals or convert radicals into less active forms, preventing cell damages [36]. Indeed, the extract loaded in hyalurosomes avoided cell death caused by hydrogen peroxide, thus ensuring the maintenance of healthy condition at all the tested dilutions (from 10 to 0.01 µg/mL of the extract), while the free extract (unloaded) had a low protective activity which was slightly evident only when using the higher concentrations.…”

Section: Discussionmentioning

confidence: 99%

Formulation and Testing of Antioxidant and Protective Effect of Hyalurosomes Loading Extract Rich in Rosmarinic Acid Biotechnologically Produced from Lavandula angustifolia Miller

et al. 2022

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Culture of plant cells or tissues is a scalable, sustainable, and environmentally friendly approach to obtain extracts and secondary metabolites of uniform quality that can be continuously supplied in controlled conditions, independent of geographical and seasonal variations, environmental factors, and negative biological influences. In addition, tissues and cells can be extracted/obtained from the by-products of other industrial cultivations such as that of Lavandula angustifolia Miller (L. angustifolia), which is largely cultivated for the collection of flowers. Given that, an extract rich in rosmarinic acid was biotechnologically produced starting from cell suspension of L. angustifolia, which was then loaded in hyalurosomes, special phospholipid vesicles enriched with sodium hyaluronate, which in turn are capable of both immobilizing and stabilizing the system. These vesicles have demonstrated to be good candidates for skin delivery as their high viscosity favors their residence at the application site, thus promoting their interaction with the skin components. The main physico-chemical and technological characteristics of vesicles (i.e., mean diameter, polydispersity index, zeta potential and entrapment efficiency of extract in vesicles) were measured along with their biological properties in vitro: biocompatibility against fibroblasts and ability to protect the cells from oxidative stress induced by hydrogen peroxide. Overall, preliminary results disclosed the promising properties of obtained formulations to be used for the treatment of skin diseases associated with oxidative stress and inflammation.

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Systematic modulation of the lipid composition enables the tuning of liposome cellular uptake

et al. 2023

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How stereochemistry of lipid components can affect lipid organization and the route of liposome internalization into cells

Abstract: Lipid stereochemistry was shown to drive cell internalization of liposomes through either clathrin or caveolae. Molecular dynamic simulations highlighted molecular interactions that affect physicochemical and biological features of liposomes.

Cited by 9 publications

References 83 publications

Asynchronous Reciprocal Coupling of Martini 2.2 Coarse-Grained and CHARMM36 All-Atom Simulations in an Automated Multiscale Framework

Asynchronous Reciprocal Coupling of Martini 2.2 Coarse-Grained and CHARMM36 All-Atom Simulations in an Automated Multiscale Framework

Formulation and Testing of Antioxidant and Protective Effect of Hyalurosomes Loading Extract Rich in Rosmarinic Acid Biotechnologically Produced from Lavandula angustifolia Miller

Systematic modulation of the lipid composition enables the tuning of liposome cellular uptake

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