Single-Molecule Two-Color Coincidence Detection of Unlabeled alpha-Synuclein Aggregates

Protein misfolding and aggregation into oligomeric and fibrillar structures is a common feature of many neurogenerative disorders. Single-molecule techniques have enabled characterization of these lowly abundant, highly heterogeneous protein aggregates, previously inaccessible using ensemble averaging techniques. However, they usually rely on the use of recombinantly-expressed labeled protein, or on the addition of amyloid stains that are not protein-specific. To circumvent these challenges, we have made use of a high affinity antibody labeled with orthogonal fluorophores combined with fast-flow microfluidics and single-molecule confocal microscopy to specifically detect α-synuclein, the protein associated with Parkinson's disease. We used this approach to determine the number and size of α-synuclein aggregates down to picomolar concentrations in biologically relevant samples.     

Solid-State and Solution Self-assembly Properties of Mono- and Bis-acetylide RuII Complexes Bearing Hydrogen-Bonding Amide Functions

In this work, we report our latest results regarding the self-assembly properties of two Ru-acetylides complexes and their corresponding free organic ligands, in solution and in the solid state. The four compounds show mesogenic properties, which we have rationalized thanks to extensive DSC, SAXS, POM, FTIR and molecular dynamic investigations. We clearly establish that hydrogen bonds stabilize the supramolecular structures, and that introducing the metal center and its coordination sphere induces large change in the liquid crystal properties. In addition, for the monoacetylide compound Ru₂ , solution-state studies helped us rationalize its supramolecular abilities. In particular, we demonstrate that Ru₂ follows an isodesmic growth supramolecular polymerization in aromatic solvent.     

Kinetic Delay in Cooperative Supramolecular Polymerization by Redefining the Trade-Off Relationship between H-Bonds and Van der Waals/π–π Stacking Interactions

We here present how rebalancing the interplay between H-bonds and dispersive forces (Van der Waals/π–π stacking) may induce or not the generation of kinetic metastable states. In particular, we show that extending the aromatic content and favouring the interchain VdW interactions causes a delay into the cooperative supramolecular polymerization of a new family of toluene bis-amide derivatives by trapping the metastable inactive state.