UMR9187 / U1196 – Chimie, modélisation et imagerie pour la biologie

Publications de l’unité

Année de publication : 2018

Hammerer F., Poyer F., Fourmois L., Chen S., Garcia G., Teulade-Fichou M.P., Maillard P., Mahuteau-Betzer F. (2018 Jan 1)

Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two-photon photodynamic therapy

Bioorganic & Medicinal Chemistry : 26 : 107-118 : DOI : 10.1016/j.bmc.2017.11.024 En savoir plus
Résumé

The proof of concept for two-photon activated photodynamic therapy has already been achieved for cancer treatment but the efficiency of this approach still heavily relies on the availability of photosensitizers combining high two-photon absorption and biocompatibility. In this line we recently reported on a series of porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production quantum yield as well as high two-photon absorption cross-sections but with a very poor cellular internalization. We present herein new photosensitizers of the same porphyrin-triphenylamine hybrid series but bearing cationic charges which led to strongly enhanced water solubility and thus cellular penetration. In addition the new compounds have been found localized in mitochondria that are preferential target organelles for photodynamic therapy. Altogether the strongly improved properties of the new series combined with their specific mitochondrial localization lead to a significantly enhanced two-photon activated photodynamic therapy efficiency.

Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two-photon photodynamic therapy

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Verguet A., Messaoudi C., Sorzano C.O.S., Marco S. (2018 Jan 1)

Alignment of Tilt Series

Cellular Imaging : 183-207 : DOI : 10.1007/978-3-319-68997-5 En savoir plus
Résumé

Computing of three-dimensional reconstructions from images obtained by transmission electron tomography needs three main steps: data acquisition, projection alignment, and 3D reconstruction. In this chapter we will focus on the process of alignment moving from the justification of its need to the study of the different classical approaches (cross-correlation, use of added fiducial markers) that have been commonly used in this alignment process. We will also discuss the most recent algorithms (multiscale registration, invariant feature recognition) as they have been adapted to Electron Tomography and improved to increase the accuracy and resolution of the final tomograms.

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Année de publication : 2017

Trépout S., Tassin A.M., Marco S., Bastin P. (2017 Dec 14)

STEM tomography analysis of the trypanosome transition zone

Journal of Structural Biology : In press, corrected proof : - : DOI : 10.1016/j.jsb.2017.12.005 En savoir plus
Résumé

The protist Trypanosoma brucei is an emerging model for the study of cilia and flagella. Here, we used scanning transmission electron microscopy (STEM) tomography to describe the structure of the trypanosome transition zone (TZ). At the base of the TZ, nine transition fibres irradiate from the B microtubule of each doublet towards the membrane. The TZ adopts a 9+0 structure throughout its length of ∼300 nm and its lumen contains an electron-dense structure. The proximal portion of the TZ has an invariant length of 150 nm and is characterised by a collarette surrounding the membrane and the presence of electron-dense material between the membrane and the doublets. The distal portion exhibits more length variation (from 55 to 235 nm) and contains typical Y-links. STEM analysis revealed a more complex organisation of the Y-links compared to what was reported by conventional transmission electron microscopy. Observation of the very early phase of flagellum assembly demonstrated that the proximal portion and the collarette are assembled early during construction. The presence of the flagella connector that maintains the tip of the new flagellum to the side of the old was confirmed and additional filamentous structures making contact with the membrane of the flagellar pocket were also detected. The structure and potential functions of the TZ in trypanosomes are discussed, as well as its mode of assembly.

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Slodzian G., Wu T.D., Duprat J., Engrand C., Guerquin-Kern J.L. (2017 Dec 1)

Dynamic transfer applied to secondary ion imaging over large scanned fields with the nanoSIMS 50 at high mass resolution

Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms : 412 : 123-173 : DOI : 10.1016/j.nimb.2017.06.019 En savoir plus
Résumé

Dynamic transfer is an adaptive optical approach used for coupling a scanning ion probe with the mass spectrometer designed for analyzing sputtered ions emanating from the probe impact. Its tuning is of crucial importance for getting uniform signal collection over large scanning fields and therefore scanning images free of vignetting in a context of high mass resolution. Revisiting the optical design of the NanoSIMS 50 instrument, where the same set of lenses focuses the primary ion probe on the sample and collects secondary ions from the sample, led us to develop novel experimental procedures to achieve dynamic transfer tuning and overcome instrumental imperfections. It is the case for scanning distortion that may be induced by the octopole used for correcting probe astigmatism and may cause irreducible vignetting on scanning images. We show that it is possible to develop complete tuning procedures by compromising temporarily on the sharpness of the probe focus. Most importantly, we show that, in a context of high mass resolution, the transfer does not significantly disturb isotopic ratios over large scanned fields provided external coils are properly adjusted to compensate ambient magnetic fields.

Deepening the procedures led us to demonstrate that the scanning center of the probe may not coincide with the imaging center of COOL, Coaxial Objective Lenses forming the probe and extracting secondary ions. We have checked that bringing those two centers into coincidence resulted in a better image quality over large fields.

In the present work, we show how to handle the secondary beam in order to position it before it enters the spectrometer. That capability is essential for optimizing transmission at high mass resolution by aligning the secondary beam axis on a given entrance axis of the spectrometer.

These results led us to propose several instrumental improvements including the crucial interest of an additional octopole upstream in the primary ion probe column to prevent scanning distortion when performing astigmatism correction and the possibility of offsetting primary beam deviating plates to bring scanning and imaging centers in coincidence.

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