Kinetically controlled coassembly of multichromophoric peptide hydrogelators and the impacts on energy transport

We report a peptide-based multichromophoric hydrogelator system, wherein π-electron units with different inherent spectral energies are spatially controlled within peptidic 1-D nanostructures to create localized energy gradients in aqueous environments. This is accomplished by mixing different π-conjugated peptides prior to initiating self-assembly through solution acidification. We can vary the kinetics of the assembly and the degree of self-sorting through the choice of the assembly trigger, which changes the kinetics of acidification. The hydrolysis of glucono-δ-lactone (GdL) provides a slow pH drop that allows for stepwise triggering of peptide components into essentially self-sorted nanostructures based on subtle pKa differences, whereas HCl addition leads to a rapid formation of mixed components within a nanostructure. Using 1H NMR spectroscopy and fiber X-ray diffraction, we determine the conditions and peptide mixtures that favor self-sorting or intimate comixing. Photophysical investigations in the solution phase provide insight into the correlation of energy-transport processes occurring within the assemblies to the structural organization of the π-systems

Alzheimer's disease-like paired helical filament assembly from truncated tau protein is independent of disulphide cross-linking

Abstract Alzheimer's disease is characterised by the self-assembly of tau and amyloid β proteins into oligomers and fibrils. Tau protein assembles into paired helical filaments (PHFs) that constitute the neurofibrillary tangles observed in neuronal cell bodies in individuals with Alzheimer's disease. The mechanism of initiation of tau assembly into {PHFs} is not well understood. Here we report that a truncated 95-amino acid tau fragment (corresponding to residues 297-391 of full-length tau) assembles into PHF-like fibrils in vitro without the need for other additives to initiate or template the process. Using electron microscopy, circular dichroism and X-ray fibre diffraction, we have characterised the structure of the fibrils formed from truncated tau for the first time. To explore the contribution of disulphide formation to fibril formation, we have compared the assembly of tau(297-391) under reduced and non-reducing conditions and for truncated tau carrying a {C322A} substitution. We show that disulphide bond formation inhibits assembly and that the {C322A} variant rapidly forms long and highly ordered PHFs

GrailQuest & HERMES: Hunting for Gravitational Wave Electromagnetic Counterparts and Probing Space-Time Quantum Foam

Within Quantum Gravity theories, different models for space-time quantisation predict an energy dependent speed for photons. Although the predicted discrepancies are minuscule, GRB, occurring at cosmological distances, could be used to detect this signature of space-time granularity with a new concept of modular observatory of huge overall collecting area consisting in a fleet of small satellites in low orbits, with sub-microsecond time resolution and wide energy band (keV-MeV). The enormous number of collected photons will allow to effectively search these energy dependent delays. Moreover, GrailQuest will allow to perform temporal triangulation of high signal-to-noise impulsive events with arc-second positional accuracies: an extraordinary sensitive X-ray/Gamma all-sky monitor crucial for hunting the elusive electromagnetic counterparts of GW. A pathfinder of GrailQuest is already under development through the HERMES project: a fleet of six 3U cube-sats to be launched by 2021/22

PROTEIN MODELS: A COMPUTATIONAL APPROACH TO FOLDING AND AGGREGATION PHENOMENA

Square lattice protein models are used to study the competition between folding and aggregation phenomena. The problem is approached by considering Metropolis Monte Carlo simulations of non-isolated lattice protein models; different protein molecules can interact each other and, in competition with folding, can aggregate by forming dimers. The calculations take in exam the behavior of three types of proteins: a) proteins with a very well designed sequence (good folders); b) proteins which folding kinetics present kinetic partitioning effects (intermediate folders); c) small proteins with native states having the geometry of pure secondary structure motives (like alpha helices or beta sheets). The results show that good folders very rarely form aggregates; on the contrary, in almost all considered cases, intermediate folders display high tendency to form dimers. Finally, alpha helices display a low tendency to aggregate in comparison to that found for beta-sheets. However, also for these systems, structural intermediates in the folding kinetics can strongly influence the aggregation tendency