Sujets

In line with the team’s ambition to develop innovative tools for manipulating biological systems, our research focuses on the design of responsive macromolecules based on comb-like copolymers. On one hand, these polymers are used to engineer stimuli-responsive coatings that enable control over cell adhesion, with current efforts emphasizing light as an external trigger (F. Dalier, ACS Applied Materials & Interfaces, 2018; G. Boniello, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2019). On the other hand, they are employed in the design of responsive capsules aimed at achieving spatiotemporal control over drug delivery to trigger specific cellular events (L Sixdenier, ACS Macro Letters, 2022; L Sixdenier, The Journal of Physical Chemistry Letters, 2023).

While present at relatively low concentrations compared to organic species, endogenous metals are involved as cellular actuators such as enzymes or transcription factors. Their tight regulation at the cellular and organism levels is required in many biological processes, ranging from physiological to pathological ones. We develop and implement innovative and non-conventional approaches to achieve metal quantification, localisation and bioavailability in a variety of biological models and physiopathological contexts. Our projects cover elemental metal detection particularly to improve sample preparation procedures, together with genetically-encoded systems to sense metal levels inside biological samples. Collaborators: - O. Espeli & S. Rimski, Collège de France, Paris - P. Bost, Institut Curie, Paris.

Tissue repair and embryogenesis both involve variations in H2O2 levels. The team works on zebrafish, which is a transparent organism in which optical probes can be followed. Tracking H2O2 levels in zebrafish expressing a genetically encoded H2O2 probe (HyPer) is possible, for example at the scar of a severed fin or during embryogenesis. We study the role of redox signaling during regeneration in adult zebrafish: the distribution of H2O2 shows an increasing concentration gradient towards the scar. H2O2 distribution also varies during morphogenesis, with waves in time and space. Collaborators: - S. Thenet & V. Carrière, CRSA, Paris References: 21 C. Rampon et al., Antioxidants, 2018, 7, 159. 22 M. Thauvin et al., Journal of Cell Science, 2022, 135, jcs259664. 23 C. Gauron et al., Dev Biol, 2016, 414, 133–141.

### Chemogenetic tools to observe cell biology at various scale in space and time Fluorescent reporters and sensors play a central role in biological and medical research. Targeted to specific biomolecules or cells, they allow the visualization of the mechanisms that govern cells and organisms in real time. Recently, chemogenetic reporters composed of organic chromophores interacting with a protein moiety have challenged the hegemony of fluorescent proteins classically used in Cell Biology. Combining the advantage of synthetic fluorophores with the targeting selectivity of genetically encoded systems, these chemogenetic reporters open new perspectives for the study of cellular processes. Our team has recently introduced a new class of chemogenetic fluorescent reporters, called FASTs (fluorescence-activating and absorption-shifting tags), which allow the visualization of gene expression and protein localization in living cells and organisms (PNAS 2016, Chem. Sci. 2017, Bioconjug. Chem. 2018, Angew. Chem. 2020, Nat. Chem. Biol. 2021, Nat. Commun. 2021, Acc. Chem. Res. 2022). Engineered using a concerted strategy of molecular engineering and directed protein evolution, FASTs are small protein tags that bind and stabilize the fluorescent state of fluorogenic chromophores. Dark when free in solution or cells, these so-called fluorogens allow the imaging of FAST-tagged proteins with very high contrast without the need for washing. FAST and its variants have proved to be a useful tool that is compatible with multiple microscopy modalities and model organisms. It excels in applications in oxygen-poor environments or in situations where the lack of delay in the formation of a fluorescent complex allows the detection of rapid biological events. Recently, we expanded our toolbox with near-infrared chemogenetic fluorescent reporters (Nat. Commun. 2025) for advanced in vivo imaging and fluorescence lifetime-modulating tags for highly multiplexed imaging in cells and organisms (Advanced Science 2024). The modular nature of these reporters allowed us furthermore to design biosensors for the detection of key metabolites (ACS Chem. Biol 2018, ACS Sensors 2023). In addition, bisection of FASTs into two complementary fragments enabled the design of split fluorescent reporters with rapid and reversible complementation for the imaging of dynamic protein-protein interactions (Nat. Commun. 2019, ACS Chem. Biol. 2024, ChemBioChem 2025). This latter technology holds great potential for developing screening strategies to identify stabilizers or disruptors of protein-protein interactions, which could have therapeutic applications. Recently, splitFAST has been successfully employed to probe the dynamics of membrane contact sites (Nat. Commun. 2024) and has been extended to a tripartite version for the detection of ternary interactions (Nat. Commun. 2025), further expanding its versatility and utility in biological research. Our current research interests focus on: 1. innovative chemogenetic optical reporters and sensors for imaging cell biology at various scale in space and time using advanced microscopy. 2. generic tools to image endogenous proteins to systematically study protein function in a native cellular background. 3. optical sensors of protein-protein, organelle-organelle, and cell-cell interactions. 4. optical mechanosensors for measuring forces in cells. ### Chemogenetic tools to control cellular functions in cell biology and biomedicine The specificity of cellular functions results from the spatial and temporal organization of functionally interacting proteins. Various strategies are used by cells to achieve specificity including protein compartmentalization in organelles, protein colocalization on membranes, or assembly of protein complexes mediated by specific scaffolds. Such spatial organization enables to increase effective molarity in biochemical processes and is essential for key cellular processes such as gene regulation, protein transport, organelle transport and positioning, signal transduction, metabolism, immune response or cell-cell communications. To study and understand the role of the spatiotemporal organization of proteins in these processes, we recently introduced CATCHFIRE (Chemically Assisted Tethering of CHimera by Fluorogenic Induced Recognition), a chemogenetic tool enabling to control the physical proximity of proteins and quantify this proximity (Nat. Methods 2023). This tool relies on the genetic fusion of two small dimerization domains that can interact together in presence of a fluorogenic inducer of dimerization that fluoresces upon formation of the ternary assembly, allowing real-time monitoring of chemically induced proximity. This technology allows the fine control of biological processes through chemically induced proximity of proteins. Our current research interests focus on: 1. Chemically induced proximity tools to manipulate and control biochemical processes for cell biology applications. 2. Small-molecule-based control modules for applications in cell biology and cell therapy.

We investigate chemical reactivity in solution and at aqueous interfaces by combining theory, DFT-based or machine-learning molecular dynamics and enhanced sampling to reveal how solvent structure and dynamics control reaction mechanisms and rates. Building on detailed analyses of solution and interfacial water structure and dynamics, we show how hydrogen-bond rearrangements and electrostatic heterogeneity impact reactivity at aqueous interfaces and in confined environments. Recent applications include acid-base reactions relevant to atmospheric chemistry and how controlling solvation properties at electrochemical interfaces can impact chemical reactivity.

Our team specializes in the development of cutting-edge chemical tools to enable high-precision biological imaging. By integrating expertise in chemical biology, organic synthesis, and photophysics, we design and optimize small molecule probes that push the boundaries of live-cell and super-resolution microscopy. ### Key Research Areas #### Fluorogenic Bioorthogonal Reactions for Biomolecule Labeling Bioorthogonal chemistry allows the selective labeling of biomolecules in complex biological environments. Our team is pioneering the development of fluorogenic bioorthogonal reactions, where two non-fluorescent reagents react to form a fluorescent product. This approach ensures high contrast and spatiotemporal precision in labeling, eliminating background fluorescence and enabling real-time imaging without washing steps. Our work focuses on expanding the toolkit for near-infrared probes and improving the quantification of reaction efficiency, with broad applications in live-cell imaging. #### Blinking Dyes for Super-Resolution Microscopy Super-resolution microscopy has transformed our ability to visualize cellular structures at the nanoscale. We are developing blinking dyes based on the BODIPY scaffold, which exhibit exceptional photophysical properties, including high quantum yields, narrow emission bands, and low toxicity. By fine-tuning their structure, we control their on/off equilibrium, making them ideal for single-molecule localization microscopy (SMLM). This technique enables nanometric precision in imaging, providing unprecedented insights into cellular organization and dynamics. ### Our Approach - Innovative Synthesis: Design and synthesis of novel fluorescent probes tailored for specific imaging applications. - Photophysical Optimization: Tuning probe properties to enhance contrast, stability, and compatibility with live-cell environments. - Biological Validation: Characterization of probes in physiological conditions to ensure reliability and performance.

Fluorescence imaging is widely used in the life sciences to study biological processes, most often with exogenous fluorescent probes. However, the illumination required to excite these probes also induces photochemical reactions whose mechanisms are often poorly understood. A rigorous understanding of probe photochemistry is essential for their proper use in imaging, for controlling photochemical reactions, and for improving probe design. Since the advent of super-resolution microscopy, probe photochemistry has also been a continuous source of inspiration for the development of innovative imaging methods. Our work on fluorescent probes therefore combines fundamental mechanistic studies with methodological developments in imaging. Recent work has focused on fluorescent proteins of the GFP family, which are the main probes used for in vivo imaging. ### 1. Reverse Intersystem Crossing to Reduce Photobleaching and Phototoxicity Photobleaching and phototoxicity are among the principal limitations of fluorescence imaging. Both processes are generally understood to involve the triplet excited states of fluorescent probes as key intermediates. We recently introduced a method to reduce photobleaching of fluorescent proteins and the associated phototoxicity in vivo under wide-field illumination (Ludvikova *et al.*, *Nature Biotechnology*, 2024). This approach exploits reverse intersystem crossing (RISC) to depopulate triplet states using near-infrared light. The method can be readily implemented on commercial wide-field microscopes and is effective in both eukaryotic and prokaryotic cells for a broad range of green and yellow fluorescent proteins. Ongoing work aims to extend this strategy to other classes of fluorophores and imaging modalities.  ### 2. Mechanisms of Fluorescent Protein Photoswitching Reversibly photoswitchable fluorescent proteins (RSFPs) are central probes in super-resolution microscopy and other advanced imaging techniques. X-ray crystallography has revealed two possible photoswitching mechanisms: cis–trans isomerisation of the chromophore coupled to proton transfer, or the reversible addition of a water molecule to the chromophore. We have characterised these two mechanisms in detail using time-resolved spectroscopy down to the femtosecond timescale, focusing on the RSFPs Dreiklang (Renouard *et al.*, *J. Phys. Chem. Lett.*, 2023; Lacombat *et al.*, *J. Phys. Chem. Lett.*, 2017) and Dronpa (Yadav *et al.*, *J. Phys. Chem. B*, 2015). This work has enabled us to establish a comprehensive mechanistic picture of the elementary steps and characteristic time scales governing fluorescent protein photoswitching. ### Experimental Capabilities We are equipped for mechanistic photochemistry studies with a home-built femtosecond transient absorption spectroscopy setup (excitation 300–700 nm, broadband probe 300–1100 nm, time window 100 fs–3 ns) and a nanosecond optical parametric oscillator (excitation 190–2500 nm) for time-resolved fluorescence and micro- to millisecond transient absorption measurements. These instruments are also routinely used in collaborative projects to investigate molecular systems beyond fluorescent proteins. ### Selected References - **Near-infrared co-illumination of fluorescent proteins reduces photobleaching and phototoxicity**, L. Ludvikova, E. Simon, M. Deygas, T. Panier, M.-A. Plamont, J. Ollion, A. Tebo, M. Piel, L. Jullien, L. Robert, T. Le Saux, A. Espagne, *Nature Biotechnology*, 2024, **42**, 872–876. [Link] - **Multiscale transient absorption study of the fluorescent protein Dreiklang and two point variants provides insight into photoswitching and non-productive reaction pathways**, E. Renouard, M. Nowinska, F. Lacombat, P. Plaza, P. Müller, A. Espagne, *The Journal of Physical Chemistry Letters*, 2023, **14**, 6477–6485. [Link] - **Ultrafast oxidation of a tyrosine by proton-coupled electron transfer promotes light activation of an animal-like cryptochrome**, F. Lacombat, A. Espagne, N. Dozova, P. Plaza, P. Müller, K. Brettel, S. Franz-Badur, L.-O. Essen, *Journal of the American Chemical Society*, 2019, **141**, 13394–13409. [Link] - **Photosensitized oxidative addition to gold(I) enables alkynylative cyclization of o-alkylnylphenols with iodoalkynes**, Z. Xia, V. Corcé, F. Zhao, C. Przybylski, A. Espagne, L. Jullien, T. Le Saux, Y. Gimbert, H. Dossmann, V. Mouriès-Mansuy, C. Ollivier, L. Fensterbank, *Nature Chemistry*, 2019, **11**, 797–805. [Link] - **Photoinduced chromophore hydration in the fluorescent protein Dreiklang is triggered by ultrafast excited-state proton transfer coupled to a low-frequency vibration**, F. Lacombat, P. Plaza, M.-A. Plamont, A. Espagne, *The Journal of Physical Chemistry Letters*, 2017, **8**, 1489–1495. [Link] - **Real-time monitoring of chromophore isomerization and deprotonation during the photoactivation of the fluorescent protein Dronpa**, D. Yadav, F. Lacombat, N. Dozova, F. Rappaport, P. Plaza, A. Espagne, *The Journal of Physical Chemistry B*, 2015, **119**, 2404–2414. [Link]

When practiced at its interface with biology and physics, chemistry offers more than a toolkit for labeling biomolecules or analyzing cellular composition. It provides a distinct molecular perspective that enables quantitative interrogation of interactions and kinetic analysis of exquisitely complex reaction networks. This perspective underlies our research activity: we introduce and implement chemical concepts and tools to interrogate and manipulate biological systems. More specifically, our recent work focuses on the development of photoactive organic probes and reactivity-based protocols for highly selective analyses and imaging in live cells as well as in photosynthetic organisms (microalgae and plants). ### Recent References - R. Chouket, A. Pellissier-Tanon, A. Lahlou, R. Zhang, D. Kim, M.-A. Plamont, M. Zhang, X. Zhang, P. Xu, N. Desprat, D. Bourgeois, A. Espagne, A. Lemarchand, T. Le Saux, L. Jullien, **Extra kinetic dimensions for label discrimination**, *Nature Communications*, 2022, **13**, 1482. - A. Lahlou, H. Sepasi Tehrani, I. Coghill, Y. Shpinov, M. Mandal, M.-A. Plamont, I. Aujard, Y. Niu, L. Nedbal, D. Lazár, P. Mahou, W. Supatto, E. Beaurepaire, I. Eisenmann, N. Desprat, V. Croquette, R. Jeanneret, T. Le Saux, L. Jullien, *Nature Methods*, 2023, **20**(12), 1930–1938. - H. Merceron, I. Coghill, A. Lahlou, M.-A. Plamont, L. Jullien, T. Le Saux, **Periodic Light Modulations for Low-Cost Wide-Field Imaging of Luminescence Kinetics Under Ambient Light**, *Advanced Science*, 2025, **12**(10), 2413291. - H. Merceron, E. Israelievitch, V. Rollot, T. Villarubias, X. Xie, T. Le Saux, K. Benzerara, F. Guyot, A. Boulouis, E. Marie-Bègue, L. Thouin, L. Jullien, **A Reaction–Diffusion Frame for Accessing Metabolic O₂ Fluxes in Single Microalgal Cells with Low-Cost Wide-Field Imaging of Nanosensor Luminescence Lifetime**, *Advanced Science*, 2025, **12**(42), e10903. - Y. Shpinov, M. Mandal, V. van Deuren, A. Lahlou, M. Le Bec, R. Chouket, C. Hadj Moussa, C. Bonin, H. Sepasi Tehrani, I. Coghill, L. El Hajji, K. Ounoughi, J. Franco Pinto, M.-A. Plamont, P. Pelupessy, I. Ayala, F. Perez, I. Aujard, T. Le Saux, A. Gautier, P. Dedecker, B. Brutscher, L. Jullien, **Photoejection turns non-covalent fluorescent tags into negative reversible photoswitchers**, *bioRxiv*, 2025, doi: 10.1101/2025.12.05.692574.

We develop machine-learning interatomic potentials that bring near-quantum chemical accuracy to molecular simulations of reactive processes in condensed phases, from bulk water and interfaces to complex chemical environments, while reaching time and length scales inaccessible to direct ab initio dynamics. A key focus of our work is data-efficient training (active learning) and the tight coupling of machine learning potentials with enhanced and path-sampling methods to reveal mechanisms, rate-limiting steps, and rare reactive events. Recent applications include uncovering the molecular mechanism of proton transport in water, achieving microsecond reactive sampling to dissect prebiotic reaction pathways relevant to origins-of-life chemistry, and the prediction of reactive properties in the low-data regime. These advances open a route to predictive, mechanistic modeling that can guide the design of new catalysts by connecting atomistic dynamics directly to reactivity and selectivity.

### 1. New Tools to Study Phase Separation in Living Cells Biomolecular condensates formed by intracellular phase separation organize essential cellular processes, from gene regulation to metabolism. While phase separation is now recognized as a key organizing principle, the rules governing condensate composition, dynamics, and function remain poorly understood. To address this, we develop engineered artificial scaffolds that form phase-separated condensates directly in living cells (Cochard et al., *EMBO J.* 2023; *Biophys. J.* 2022). This bottom-up approach enables precise control of condensate properties within the native cellular environment, allowing us to engineer new cellular functions and model pathological condensates linked to aging and disease. ### 2. Harnessing Biochemical Processes with Synthetic Condensates Cellular compartmentalization relies on dynamic exchange between organelles, yet existing perturbation methods lack specificity and control. We developed **ControLD**, a strategy to physically isolate lipid droplets—key organelles in energy storage and stress protection (Amari et al., *Nat. Chem. Biol.* 2025). ControLD uses engineered phase-separating proteins to form a reversible meshwork on lipid droplets, selectively blocking their metabolism and enabling direct interrogation of organelle communication. ### 3. Biophysics of Proteinopathies in Neurodegeneration and Cancer Many neurodegenerative diseases arise from the conversion of soluble proteins into pathological aggregates, including α-synuclein, TAU, and TDP-43. How these aggregates drive cellular dysfunction remains unclear. We develop cellular models of disease-relevant condensates and aggregation. Recently, we showed that spreading α-synuclein aggregates convert liquid α-synuclein condensates into amyloids (Piroska et al., 2025), providing a controlled system to study pathogenic aggregation mechanisms. ### Recent References - Cochard A., Safieddine A., Combe P., Benassy M.-N., Weil D., Gueroui Z., **Condensate functionalization with motors directs their nucleation in space and allows manipulating RNA localization**, *The EMBO Journal*, 2023. https://doi.org/10.15252/embj.2023114106 - Cochard A., Garcia-Jove Navarro M., Kashida S., Kress M., Weil D., Gueroui Z., **RNA at the surface of phase-separated condensates impacts their size and number**, *Biophysical Journal*, 2022. https://doi.org/10.1016/j.bpj.2022.03.032 - Amari C., Simon D., Bellon T., Plamont M.-A., Thiam A. R., Gueroui Z., **Controlling lipid droplet dynamics via tether condensates**, *Nature Chemical Biology*, 2025. https://www.nature.com/articles/s41589-025-01915-2 - Piroska L., Fenyi A., Thomas S., Plamont M.-A., Redeker V., Melki R., Gueroui Z., **α-synuclein liquid condensates fuel fibrillar α-synuclein growth**, *Science Advances*, 2023. https://www.science.org/doi/full/10.1126/sciadv.adg5663

Sustainable chemical synthesis design hinges on efficiency and deep mechanistic insight-two intimately linked principles. Our research focuses on the **development** **of advanced catalytic strategies**, encompassing transition metal catalysis, organocatalysis, photocatalysis and electrocatalysis. We design and implement versatile **multicomponent reactions** to access complex molecular architectures in a step- and atom-economical fashion. We perform **in-depth mechanistic investigations** using complementary experimental and analytical techniques, with a particular emphasis on elucidating the behavior of metal-catalyzed transformations. These studies guide the rational tuning of catalysts, conditions and reactor setups toward more robust and sustainable processes. Most recently, we have integrated **machine learning** tools to accelerate reaction optimization and guide catalyst and condition selection. This data-driven approach uncovers hidden reactivity patterns across our multicomponent and catalytic manifolds, thereby streamlining synthetic planning. Collectively, these efforts **expand the synthetic chemist's toolkit through rational design, enabling more efficient and sustainable routes to valuable molecular targets**.

The group uses molecular chemistry, chemical biology and biophysical chemistry to design responsive (supra)molecular tools to visualize and study biological processes with a strong emphasis on the development of fluorescent probes for bioimaging.  ### Chemogenetic probes and sensors to visualize cellular biochemistry Hybrid chemogenetic probes associating a genetically-encoded protein and a small molecular probe are a versatile approach for bioimaging that combine the selectivity of the genetic encoding with the flexibility of organic fluorophore design. Using the HaloTag technology, we have design a series of fluorogenic probes based on dipolar molecular rotors. These small molecules combine ease of synthesis, wavelength tunability, and strong fluorescence activation in presence of the HaloTag protein allowing wash-free imaging of subcellular organelles in live cells.^\[1-4\] We then adapted these fluorogenic scaffolds to yield genetically targeted sensors for subcellular calcium imaging and to follow protein exocytosis.^\[5-6\] Ongoing projects involve the development of Zn²⁺ and redox fluorescent sensors.^\[7\] We are also interested in the design of red-shifted bioluminescent reporters as an alternative to fluorescence imaging. **References:** \[1\] S. Bachollet, C. Addi, N. Pietrancosta, J.-M. M. Mallet, B. Dumat, _Chem. - A Eur. J._ **2020**, _26_, 14467-14473. \[2\] S. Bachollet, Y. Shpinov, F. Broch, H. Benaissa, A. Gautier, N. Pietrancosta, J.-M. Mallet, B. Dumat, _Org. Biomol. Chem._ **2022**, _20_, 3619-3628. \[3\] J. Coïs, S. Bachollet, L. Sanchez, N. Pietrancosta, V. Vialou, J. M. Mallet, B. Dumat, _Chem. - A Eur. J._ **2024**, _30_, e202400641. \[4\] B. Dumat, C. Chieffo, _Chem. - A Eur. J._ **2025**, _31_, e202404077. \[5\] S. Bachollet, N. Pietrancosta, J.-M. Mallet, B. Dumat, _Chem. Commun._ **2022**, _58_, 6594-6597. \[6\] J. Coïs, M.-L. Niepon, M. Wittwer, H. Sepasi Tehrani, P. Bun, J.-M. Mallet, V. Vialou, B. Dumat, _ACS Sensors_ **2024**, _9_, 4690-4700. \[7\] M. Čížková, L. Cattiaux, J. Pandard, M. Guille-Collignon, F. Lemaître, J. Delacotte, J.-M. Mallet, E. Labbé, O. Buriez, _Electrochem. commun._ **2018**, _97_, 46-50. ### Biomimetic functionalized lipid microparticles to study phagocytosis Phagocytosis is fundamental process of innate immunity by which phagocytic cells (_e.g._ macrophages) internalize objects larger than 0.5 microns. To study its mechanism, we have designed oil-in-water emulsion droplets of micrometric size funtionnalized with tailor-made fluorescent (glyco)lipids to target lectin receptors and report on the cellular adhesion^\[8\] or subsequent pH acidification during phagosome maturation.^\[9\] Ongoing projects are aimed at further investigating enzymatic activity and recycling during the late stages of phagocytosis. **References:** \[8\] S. Michelis, C. Pompili, F. Niedergang, J. Fattaccioli, B. Dumat, J.-M. Mallet, _ACS Appl. Mater. Interfaces_ **2024**, _16_, 9669-9679. \[9\] S. MichelisH ; Uhl, F. Niedergang, J. Fattaccioli, B. Dumat, J.-M. Mallet _BiorXiv_ **2026**, 11.20.685382 ### Functionalized Polysaccharides for biological applications Polysaccharides are natural polymers, an excellent alternative to synthetic polymers. Many are commercially available (in various sizes and functions) and, thanks to their hydrophilic properties, are particularly well-suited to biological applications. We have developed modified polysaccharides for coating particles: gold nanoparticles (in collaboration with F. Carn), Mil-100 iron nanoparticles (in collaboration with C. Serre and M. Lepoitevin), and for presenting multivalent antigens (in collaboration with Anna Maria Papini and Laurence Mulard). We are also preparing dextran-based micro- and nanoparticles for the development of a vaccine targeting Shigella flexneri (in collaboration with Laurence Mulard, Institut Pasteur). Cyclodextrins are cyclic oligosaccharides known to form host-guest complexes; we use them to prepare self-assembled nanogels (collaboration with K. Bouchemal). **References:** **Selective capture of anti-N-glucosylated NTHi adhesin peptide antibodies by a multivalent dextran conjugate**; Antonio Mazzoleni, Feliciana Real Fernandez, Francesca Nuti, Roberta Lanzillo, Vincenzo Brescia Morra, Paolo Dambruoso, Monica Bertoldo, Paolo Rovero, Jean-Maurice Mallet, Anna Maria Papini _Chembiochem_ **2022**, 23, 2022 e202100515 . doi :10.1002/cbic.202100515 **Flash Colloidal Assembly in Micro Flow System** Florent Voisin, Gerald Lelong, Jean-Michel Guigner, Thomas Bizien, Jean-Maurice Mallet, Florent Carn, _ACS Appl. Nano Mater._ **2022**, 5, 5, 6964-6971. doi. /10.1021/acsanm.2c00944 **Charge-Driven Arrested Phase-Separation of Polyelectrolyte-Gold Nanoparticle Assemblies Leading to Plasmonic Oligomers;** Florent Voisin, Gerald Lelong, Jean-Michel Guigner, Thomas Bizien, Jean-Maurice Mallet, Florent Carn, _Journal of Colloid and Interface Science, 630,_ **2023**_, 355-364_, doi 10.1016/j.jcis.2022.08.076 **Self-assembly of gold nanoparticles by chitosan for improved epinephrine detection using a portable surface enhanced Raman scattering device** Antoine Dowek, Florent Voisin, Laetitia Le, Céline Tan, Jean-Maurice Mallet, Florent Carn, Eric Caudron _Talanta_ **2023**, 251, 123752; _doi_ /j.talanta.2022.123752 **Cyclodextrin-based supramolecular nanogels decorated with mannose for short peptide encapsulation** Archana Sumohan Pillai, Mohamed Achraf Ben Njima, Yasmine Ayadi, Laurent Cattiaux, Ali Ladram, Christophe Piesse, Benoit Baptiste, Jean-François Gallard, Jean-Maurice Mallet, Kawthar Bouchemal _International Journal of Pharmaceutics_, 2024 DOI:10.1016/j.ijpharm.2024.124379 ### Chemical neurosciences The **Chemical Neurosciences** thematic develops an integrated chemical biology approach to decipher and modulate synaptic mechanisms at the molecular level. It combines **rational ligand design, molecular modeling and protein-protein interaction analysis** with advanced fluorescence imaging to target key synaptic proteins. Major achievements include the **first drug-like ligands of vesicular glutamate transporters (VGLUTs)**, enabling selective modulation of glutamatergic transmission from biochemistry to in vivo behavior. We also highlight that **flexible and dynamic protein-protein interfaces**, such as dopamine-NMDA receptor heteromers, can be **pharmacologically targeted**, overturning the concept of "undruggable" synaptic complexes. Together, these results provide **innovative molecular tools and therapeutic perspectives** for neurological and psychiatric disorders. 

We develop first-principles models of molecular spectroscopies that connect measured signals directly to molecular structure, dynamics, and electronic motion in complex environments. By combining molecular dynamics with quantum-mechanical response theories, we simulate a broad range of spectroscopies. These include vibrational linear infrared, two-dimensional (2D IR) and sum-frequency generation (SFG) spectroscopies to unravel molecular ultrafast dynamics in solution and at interfaces, attosecond pump–probe spectroscopies to probe electron and nuclear dynamics in connection with high harmonic generation, and vibrational circular dichroism (VCD) modeling to link chiral spectroscopic signatures to conformational fluctuations and solvation effects in solution.

This topic focuses on the design and study of membranotropic peptides or proteins: Cell Penetrating Peptides (CPPs) or proteins, Antimicrobial Peptides (AMPs) and Antiviral Peptides (AVPs). We modify their side chains or peptide backbone to identify, at the molecular level, the structural motifs responsible for their different membranotropic activities. Our skills in microbiology and cell culture allow us to study and quantify the effect of chemical modifications of AMPs or AVPs on their biological activity. Analytical developments based on mass spectrometry (MS) or fluorometry make it possible to quantify the internalization of CPPs in cells. Calorimetry is used to evaluate the type of interaction of peptides with membrane models and we develop photolabeling approaches coupled with mass spectrometry analysis (PAL-MS) to identify the interaction partners of CPPs and AMPs in membrane models using photoactivatable CPPs, AMPs or lipids. Photoactivatable and fluorogenic probes are designed and synthesized to allow the transposition of PAL-MS on cells. **Associated methodologies:** - Affinity photolabeling (fluorogenic or not) coupled with mass spectrometry (PAL-MS) (C. Chieffo, E. Sachon, S. Sagan, A. Walrant) - Synthesis of modified peptides and lipids (F. Burlina, C. Chieffo, A. Walrant) - Quantifications based on mass spectrometry or fluorometry (F. Burlina, F. Illien, E. Sachon, S. Sagan, A. Walrant) - Formulation of artificial membranes and cell membranes mimics (C. Chieffo, F. Illien, A. Walrant) - Calorimetry (DSC, ITC) (S. Sagan, A. Walrant) - Bacterial and eucaryotic cell culture (T. Drujon, F. Illien)

The axis focuses on the design, synthesis and characterization of peptides and/or proteins modulating biological interactions. Chemical ligation methodologies are being developed for the synthesis of proteins incorporating non-canonical amino acids or post-translational modifications.  Cyclic peptides with enhanced pharmacological properties are conceived for the design of protein-protein interaction inhibitors (PPIs) in oncology and virology or as biocondensates modulators or glycosaminoglycan ligands for cell targeting. In parallel, approaches based on dynamic combinatorial chemistry (DCC) are developed for the screening and selection of constrained peptides. Large dynamic combinatorial libraries (DCL) of peptides are characterized by the means of separative techniques coupled with MS and tandem MS using various types of ions activation.  **Associated methodologies:** - Synthesis of modified amino acids, peptides and proteins on solid and in solution (F. Burlina, R. Moumné, L. Rocard) - Native chemical ligation and auxiliary-mediated ligation (F. Burlina) - Functionalization of peptides by dynamic combinatorial chemistry (R. Moumné, L. Rocard) - MS and MS/MS of polycationic, cyclic, gas-modified peptide ions (E. Sachon) - Protein production and purification (D. Ravault)

The objective of this research theme is the design of molecular vectors for the selective delivery of bioactive molecules to their target inside cells. These approaches consist on the development of modified homeoproteins of therapeutic interest; on the functionalization of molecular objects such as nanobodies, nanoparticles (gold, iron oxide and liposomes) and drugs by biomolecules (synthetic ligands for receptors, membranotropic peptides, targeting peptides, protein, ...) allowing their cellular uptake, organelle targeting and spatio or spatio-temporally precise activation and tracking inside cells. **Associated methodologies:** - Functionalization of nanoparticles (F. Burlina, C. Mansuy, R. Moumné, A. Walrant) - Protein vectorization (F. Burlina, S. Sagan, A. Walrant) - Organic synthesis for prodrug development (R. Moumné)

Vesicular exocytosis is a way of communication between the cells in many systems in our body (nervous, endocrine, immune and other systems) which involves chemical messengers (neurotransmitters or other bioactive compounds) stored in intracellular vesicles. Importance of the exocytosis studies is easily understood when noting that exocytosis is involved in a very crucial processes ensuring proper functioning of an organism and hence any abnormalities may result in various diseases (neuro-degenerative diseases is an important particular example). We study kinetics of exocytotic release in the quest of identifying general physicochemical principles underpinning exocytosis. In particular, we develop parsimonious models relating physicochemical parameters of exocytotic release with features of electrochemically acquired (notably, single cell amperometry) data.

Many practical micro- and nanoscale systems in heterogeneous catalysis, electrolyzers or electroanalytical sensing can be represented as arrays of active sites distributed randomly on inert surfaces since this allows to decrease the amount of expensive materials and often provides even better performances than solid materials owing to enhanced micro- and nanoscale diffusion rates and/or more reactive surface atoms. Those may include partially blocked electrodes, membranes or non-(electro)chemically active substrates with active/catalytic nanosites dispersed on their surface to name a few. We develop approaches to model and characterize these complex systems as well as to understand better their intrinsic properties.

We use atomistic simulations and advanced sampling to map the conformational landscapes of biomolecules (proteins, nucleic acids and their complexes) and to connect structure to function. These approaches provide a predictive framework to understand and ultimately control biomolecular flexibility, hydration, and reactivity in realistic environments relevant to biology and medicinal chemistry. Recent applications include RNA catalysis, extremophilic enzymes, allosteric regulation of proteins, DNA junctions and CO2 enzymes.

Peptidoglycan is a dynamic macromolecule that needs to be modulated along the bacterial cell cycle in order to remain protective during cell elongation and cell division. This research axis focuses on understanding the dynamics of peptidoglycan synthesis across multiple species of Gram negative and Gram positive bacteria. It aims to characterize the schematics of new peptidoglycan strands insertion in the existing mesh. We use a combination of liquid chromatography, high-resolution mass spectrometry, and fluorescence microscopy to decipher and visualize the mode of peptidoglycan expansion, in wild-type cells or in combination with drugs or mutations that affect the cell cycle. Interactions between newly synthetized peptidoglycan strands and the protective mesh are quantified by a newly developed pulse-labelling method, using stable isotopes of carbon and nitrogen. Because peptidoglycan remodeling is mediated by the coordinated action of synthetic and lytic enzymes, providing tight regulation to avoid erratic peptidoglycan lysis, this project also aims to evaluate the participation of lytic enzymes in peptidoglycan expansion. **Associated publications:** - Anoyatis-Pelé C, Bellard L, Sezonov G, Morlot C, Hugonnet JE, Arthur M. (2025). Role of endopeptidases in lateral cell wall expansion in Escherichia coli. Cell Rep, Oct 28;44(10):116389 - Liang, Y., Bellard, L., Wong, S.Y., Morlot, C., Hugonnet, J.E., Rusconi, F., and Arthur, M. (2025). Mechanism of lateral cell wall expansion at a constant diameter in Bacillus subtilis. Nat Commun, Jul 19;16(1):6671. - Liang, Y., Hugonnet, J.E., Rusconi, F., and Arthur, M. (2024). Peptidoglycan-tethered and free forms of the Braun lipoprotein are in dynamic equilibrium in Escherichia coli. Elife 12. - Atze, H., Liang, Y., Hugonnet, J.E., Gutierrez, A., Rusconi, F., and Arthur, M. (2022). Heavy isotope labeling and mass spectrometry reveal unexpected remodeling of bacterial cell wall expansion in response to drugs. Elife 11.

Antibiotics of the β-lactam family inhibit the action of transpeptidases, essential enzymes that cross-link the peptidoglycan mesh. This inhibition halts peptidoglycan expansion and accounts for bacterial growth arrest. Binding of β-lactams on transpeptidases does not inhibit the action of glycosyltransferase enzymes, that polymerize new peptidoglycan strands, leading to a futile cycle of polymerization and hydrolysis of peptidoglycan synthesis intermediates. This futile cycle triggers a cell-wide metabolic dysregulation, causing global stresses that ultimately kill the bacterium. The aim of this research axis is to elucidate the cascade of events triggered by β-lactam binding to the transpeptidase targets. We use multi-omics approaches (Tn-seq, RNA-seq, Ribosome profiling, Metabolome and Proteome analyses) to identify all the regulatory circuits affected by β-lactam exposure and the significance of potential genome-wide gene expression dysregulation. This project aims to provide an exhaustive comprehension of the mechanism of β-lactam-induced bacterial death and will contribute to identifying new strategies to optimize the bactericidal activity of these antibiotics. **Associated publications:** - Voedts H, Anoyatis-Pelé C, Langella O, Rusconi F, Hugonnet JE, Arthur M. (2024). (p)ppGpp modifies RNAP function to confer β-lactam resistance in a peptidoglycan-independent manner. Nat Microbiol. Mar;9(3):647-656. - Voedts, H., Kennedy, S.P., Sezonov, G., Arthur, M., and Hugonnet, J.E. (2022). Genome-wide identification of genes required for alternative peptidoglycan cross-linking in Escherichia coli revealed unexpected impacts of beta-lactams. Nat Commun 13, 7962.

**Narrow spectrum antibiotics** Our research aims to develop innovative antibacterial strategies that are both highly effective and respectful of the host microbiota. We are designing pathogen-specific prodrugs. These compounds are selectively activated by broad-spectrum β-lactamases produced by Gram-negative priority pathogens identified by the WHO. This project, coordinated by our team and financed by the PIA-AMR, brings together eight complementary teams from Université Paris Cité, PSL, Institut Pasteur, CEA, and CNRS, combining expertise in chemical synthesis, structural biology, biochemistry, metagenomics, and host–pathogen interactions. **Novel therapies against Mycobacterium abscessus.** Mycobacterium abscessus has emerged as a major opportunistic pathogen causing chronic lung infections in cystic fibrosis patients. These infections are extremely difficult to treat due to intrinsic multidrug resistance, with eradication rates dropping to ~25% in macrolide-resistant cases. We have demonstrated that a triple combination therapy-two β-lactams (penam and carbapenem classes) combined with a second-generation diazabicyclooctane (DBO) β-lactamase inhibitor-displays strong synergistic activity in vitro, in infected macrophages, and in a murine model. We now aim to optimize this therapeutic strategy by identifying its molecular targets and, in the longer term, by developing carbapenems and DBO derivatives specifically tailored to this pathogen. **Associated publications:** - Burke K, Herail Q, Zerguine I, Bougault C, Arthur M, Etheve-Quelquejeu M, Iannazzo L. (2025). Optimization of Prodrug Activation by Enzymatic Cleavage of the β-lactam Ring of Carbapenems. Chemistry, Aug 18;31(46):e01534 - Razew A, Herail Q, Miyachiro M, Anoyatis-Pelé C, Bougault C, Dessen A, Arthur M, Simorre JP. (2024). Monitoring Drug-Protein Interactions in the Bacterial Periplasm by Solution Nuclear Magnetic Resonance Spectroscopy. J Am Chem Soc, Apr 3;146(13):9252-9260. - Le Moigne V, Bitar M, Arthur M, Mainardi J-L, Herrmann J-L. The addition of amoxicillin improves the efficacy of the imipenem-avibactam combination against Mycobacterium abscessus in a mouse model of infection. (2025). Antimicrob Agents Chemother. 2025 Aug 6;69(8):e0053425. - Bitar M, Le Moigne V, Herrmann JL, Arthur M, Mainardi JL. In vitro, intracellular and in vivo synergy between amoxicillin, imipenem and relebactam against Mycobacterium abscessus. (2025). J Antimicrob Chemother. 2025 Jun 3;80(6):1560-1567. - Sanchez L, Bitar M, Herail Q, Dorchêne D, Hugonnet JE, Arthur M, Mainardi JL. (2024). In vitro and intracellular activity of vaborbactam combined with β-lactams against Mycobacterium abscessus. J Antimicrob Chemother. Aug 1;79(8):1914-1918.

**Mechanisms of β-lactam and glycopeptide resistance, and target inhibition.** The evolution of low-affinity penicillin-binding proteins (PBPs) underlies β-lactam resistance in Gram-positive bacteria. However, the catalytic mechanism of peptidoglycan cross-linking remains poorly characterized due to the lack of defined substrates. Using enterococci as a model, we investigate how PBPs recognize peptidoglycan precursors using synthetic substrate surrogates. Our goal is to define the structural and functional constraints governing resistance acquisition and to design robust assays for the identification of novel transpeptidase inhibitors. **Expanding the therapeutic potential of DBOs.** Diazabicyclooctanes (DBOs), such as avibactam and relebactam, were initially developed as β-lactamase inhibitors against Gram-negative pathogens. We recently demonstrated that DBOs also inhibit L,D-transpeptidases, key enzymes in mycobacterial cell wall polymerization. We aim to optimize the DBO scaffold for activity against Mycobacterium tuberculosis in collaboration with our chemistry partner, leveraging original synthetic routes that have led to two patents. **Associated publications:** - Cusumano JA, Daffinee KE, Ugalde-Silva P, Peti W, Arthur M, Desbonnet C, Rice LB, LaPlante KL, García-Solache M. Penicillin-Binding Proteins and Alternative Dual-Beta-Lactam Combinations for Serious Enterococcus faecalis Infections with Elevated Penicillin MICs. Antimicrob Agents Chemother. 2023 Feb 16;67(2):e0087122. - Hunashal Y, Kumar GS, Choy MS, D'Andréa ÉD, Da Silva Santiago A, Schoenle MV, Desbonnet C, Arthur M, Rice LB, Page R, Peti W. Molecular basis of β-lactam antibiotic resistance of ESKAPE bacterium E. faecium Penicillin Binding Protein PBP5. Nat Commun. 2023. 17;14(1):4268. doi: 10.1038/s41467-023-39966-5. - Hunashal Y, Fonvielle M, Kobayashi MT, Choy MS, Kumar GS, Silva PU, Liang Y, Desbonnet C, Rice LB, Arthur M, Page R, Peti W. Peptidoglycan recruitment by a penicillin binding protein. Nat Commun. 2025; 16(1):11244. doi: 10.1038/s41467-025-66095-y. - Edoo Z, Iannazzo L, Compain F, Li de la Sierra Gallay I, van Tilbeurgh H, Fonvielle M, Bouchet F, Le Run E, Mainardi JL, Arthur M, Ethève-Quelquejeu M, Hugonnet JE. Peptidoglycan Biosynthesis Enzymes of Mycobacteria. Chemistry. 2018; 24(32):8081-8086. doi: 10.1002/chem.201800923.

In our research group we use the alphaproteobacterium model Caulobacter crescentus to understand how bacterial cell wall and cell envelope metabolisms are genetically and functionally coordinated with cell cycle and bacterial cell pole differentiation. Indeed, C. cresentus displays an atypical asymmetric division resulting in two different daughter cells: a motile non-dividing swarmer cell and a sessile replicative stalked cell. Each of these daughter cells harbors functionalized cell pole with either a flagellum and pili or a stalk. By combining genetics, biochemical studies, and microscopy, we mainly focus on peptidoglycan metabolism which includes its synthesis, remodeling and recycling and how it is integrated to C. crescentus cell cycle.

The complexity of molecular systems accessible to NMR has increased dramatically with the advent of increasing magnetic fields (now up to 28 T for commercial systems). Yet, some properties of nuclear spins are more favorable at lower magnetic fields, typically in the range of ~1 T, the conventional fields of MRI and benchtop NMR. Here, we collaborate with the company Bruker Biospin to develop a new type of NMR spectrometer that couples two magnetic centers operating at two different magnetic fields: a high magnetic field (14 T) and a lower magnetic field (~1 T). The two magnetic centers are coupled by a sample shuttle, that can transfer the sample between the two centers in less than 100 ms. This systems allows us to manipulate nuclear spins at two different magnetic fields within a single NMR experiment.

Description DNP performed at liquid helium temperature (4.2 K) is used to drive the nuclear spins out of equilibrium up to a ≈ 80 − 90% hyperpolarized state by transferring the high polarization of unpaired electron spins through hyperfine or super-hyperfine interactions. The obtained hyperpolarized compounds can then be transferred to a solution state NMR spectrometer in dissolution-DNP (D-DNP) experiments that yield signal enhancements up to 4 orders of magnitude. The large magnetization in the NMR sample induces a significant feedback field from the detecting circuit - the improperly called “radiation damping”- and leads to nonlinear phenomena, such as sustained masers that prolong the signal coherence to tens of seconds or even hours. Alternatively, we have also generated stable and sustained masers in solution, by electronically controlling the radiation feedback phenomenon, and observed multimode NMR masers.

Dissolution Dynamic Nuclear Polarization (dDNP) provides signal enhancement in solution Nuclear Magnetic Resonance (NMR) experiments by up to four orders of magnitude. Since its introduction a couple of decades ago, it has opened new prospects, in particular for the study of fast (< ~min) chemical reaction. On the one hand, i the field of biology, it allows the observation of chemical and enzymatic reactions on (fast) physiological time scales and using nuclei of lower sensitivity. There remains a number of obstacles (technical, instrumentation related) that need to be overcome and we develop dDNP methodology to advance the approach to the stage of an analytical technique. We apply dDNP to the study of several enzymes involved in the pentose phosphate pathway and in the metabolism of glutamine, both metabolic pathways of fundamental importance. On the other hand, we apply and develop dDNP methodology for the study of chemical reactions, such as the CO2 capture and release by amine solutions, of widespread use for the storage of CO2 in the industrial context.

Nuclear spin relaxation originates from the fluctuations of interactions due to motions at the molecular scales. Relaxation rates encode precious information about these motions, such as: overall rotational diffusion, librations, jumps between distinct rotamers, etc. The information on molecular motions is only probed at the resonance frequencies of nuclear spins. Thus, a measurement at a single high-field, as possible on most NMR spectrometers, provides limited information about molecular motions. Our objective is to maximize the information from relaxation in order to probe a broad range of processes. We achieve this goal by measuring relaxation over a broad range of magnetic fields by simply moving the NMR sample in the stray field of the magnet, in a fast and controlled way, so that we can still measure high-quality spectra at high field. We develop and test a series of prototype systems with the company Bruker Biospin. We use this system to determine the internal dynamics in large enzymes to understand allosteric communication, disordered proteins to understand their weak interactions, and nucleic acids. We also exploit this system to probe interactions of small molecules with macromolecules to detect metabolite-protein interactions in biological fluids, or inhibitor-enzyme complexes.

The existence of complex environments is associated with the phenomenon of anomalous diffusion where, in particular, relevant correlation functions have power law decays with time, in contrast to the classical Brownian motion. The interior of a protein provides an illustration of such an irregular medium, and the existence of subdiffusive processes has been investigated in the context of protein dynamics using various techniques, such as fluorescence correlation spectroscopy, neutron scattering or in an NMR perspective focusing on spin relaxation. We combine approaches based on the fractional Fokker-Planck, of the generalized Langevin equation to provide tools to interpret protein dynamics in the contexts of NMR and neutron scattering experiments.

We design metal-complexes as mimics of antioxidant metalloenzymes (catalases, superoxide dismutases), to be used to rescue cells from oxidative stress. We study them in cellular models of oxidative stress. Some are low molecular weight complexes directly bio-inspired from superoxide dismutase. We have been playing with chemical design, notably modulating metal-complexes inertia to improve stability in the cell environment. We use analytical techniques in cells and cell lysates to characterize the speciation and metal exchange, the redox effect in cells as well as mitigation of the oxidative stress effect. In a second strategy, we develop a combinatorial approach to design peptide-based complexes screened for their antioxidant activity. This methodology can be further extended to other types of activities. We have a strong focus on inflammatory bowel diseases. We also develop Pt-based complexes for their anticancer activity, possibly in association with SOD mimics in the context of the reduction of anti-cancer drugs side effects, such as oxaliplatin with an efficient mitigation of peripheral neuropathy. In a continuous search to transpose the metal complexes we develop to advanced systems, new delivery approaches are explored, including micelles or bacteria. Collaborators: - R. Lobinski, IPREM, Pau - J. Vinh & G. Chiappetta, ESPCI-PSL, Paris - P. Seksik & S. Demignot, CRSA, Paris - G. Pastorin, NUS, Singapore - G. Adriani, A*STAR Singapore - W.K. Leong, NTU Singapore - R. Coriat, Institut Cochin, Paris - V. Pecoraro, U. Michigan, US - M. L. Low, UCSI, Malaisie - F. Gazeau, NABI, Paris - F. Chain, L. Bermudez & P. Langella, Micalis, Jouy-en-Josas References: 1 C. Policar et al., Comptes Rendus Chimie, 2025, 25, 397–420. 2 E. Mathieu et al., Inorg. Chem., 2017, 56, 2545–2555. 4 G. Schanne et al., Oxid. Med. Cell Longev., 2022, Article ID 3858122. 5 M. Zoumpoulaki et al., Angew. Chem. Int. Ed., 2022, e202203066. 6 M. Zoumpoulaki et al., Angew. Chem. Int. Engl., 2025, e202422644. 7 K. Coulibaly et al., Inorg. Chem., 2021, 60, 9309–9319. 8 A. Vincent et al., Chem. Commun., 2020, 56, 399–402. 9 Y. Ben Hadj Hammouda et al., Molecules, 2022, 27, 5476. 10 C. Prieux-Klotz et al., IJMS, 2022, 23, 12938. 11 M.-A. Guillaumot et al., Oncotarget, 2019, 10, 6418–6431. 12 A. Lopez-Sanchez et al., Advanced Healthcare Materials, 2025, 14, 2501847. 13 G. Schanne et al., Free Radical Research, 2025, 59, 262–273.

Re(CO)3 complexes are developed as multimodal probes to correlate fluorescence, IR-imaging and X-fluorescence imaging. These probes are easy to conjugate to any type of biomolecule that can be imaged both by IR, possibly with subcellular resolution, using near-field detection (nano-IR, AFM-IR), and by X-fluorescence. We have developed and validated a series of Re-based complexes accumulating in various organelles and that can be used as organelle trackers in non-conventional imaging techniques such as X-fluorescence imaging or IR-based imaging techniques. List of the Re-based trackers so far available: nucleus trackers, mitochondria, Golgi apparatus. Collaborators: - C. Sandt, Synchrotron SOLEIL, St Aubin - K. Medjoubi, A. Somogyi, Synchrotron SOLEIL, St Aubin - C. Aimé, CPCV, Paris - A. Deniset & A. Dazzi, ICP, Saclay - M. Coogan, Univ. Lancaster, UK - O. Espeli, Collège de France, Paris References: 14 S. Clède and C. Policar, Chem. Eur. J., 2015, 21, 942–958. 15 C. Policar et al., C.R. Chim., 2024, 27, 1–25. 16 S. Hostachy et al., Chem. Sci., 2018, 9, 4483–4487. 17 S. Clède et al., Chem. Commun., 2015, 51, 2687–2689. 18 C. Policar et al., Angew. Chem. Int. Ed., 2011, 50, 860–864. 19 G. Schanne et al., Inorg. Chem. Front., 2021, 8, 3905–3915. 20 S. Clède et al., Chem. Commun., 2012, 48, 7729–7731.

Our research team focuses on membrane-peptide interactions, particularly elucidating the structural and functional mechanisms of membranotropic peptides, including cell-penetrating peptides (CPPs) and natural or synthetic antimicrobial peptides (AMPs), as well as membrane-associated proteins like TSPO (Translocator Protein). By combining advanced spectroscopic techniques, molecular dynamics (MD) simulations, and innovative membrane models, we aim to understand how these peptides and proteins interact with biological membranes at the atomic and molecular levels. This knowledge is critical for developing targeted therapeutic strategies and novel drug delivery systems.