Cucurbit[7]uril Macrocyclic Sensors for Optical Fingerprinting: Predicting Protein Structural Changes to Identifying Disease-Specific Amyloid Assemblies.

In a three-dimensional (3D) representation, each protein molecule displays a specific pattern of chemical and topological features, which are altered during its misfolding and aggregation pathway. Generating a recognizable fingerprint from such features could provide an enticing approach not only to identify these biomolecules but also to gain clues regarding their folding state and the occurrence of pathologically lethal misfolded aggregates. We report here a universal strategy to generate a fluorescent fingerprint from biomolecules by employing the pan-selective molecular recognition feature of a cucurbit[7]uril (CB[7]) macrocyclic receptor. We implemented a direct sensing strategy by covalently tethering CB[7] with a library of fluorescent reporters. When CB[7] recognizes the chemical and geometrical features of a biomolecule, it brings the tethered fluorophore into the vicinity, concomitantly reporting the nature of its binding microenvironment through a change in their optical signature. The photophysical properties of the fluorophores allow a multitude of probing modes, while their structural features provide additional binding diversity, generating a distinct fluorescence fingerprint from the biomolecule. We first used this strategy to rapidly discriminate a diverse range of protein analytes. The macrocyclic sensor was then applied to probe conformational changes in the protein structure and identify the formation of oligomeric and fibrillar species from misfolded proteins. Notably, the sensor system allowed us to differentiate between different self-assembled forms of the disease-specific amyloid-ß (Aß) aggregates and segregated them from other generic amyloid structures with a 100% identification accuracy. Ultimately, this sensor system predicted clinically relevant changes by fingerprinting serum samples from a cohort of pregnant women.

Thickness-Dependent Domain Relaxation Dynamics Study in Epitaxial K0.5Na0.5NbO3 Ferroelectric Thin Films.

We explored the time dependence of the nanoscale domain relaxation mechanism in epitaxial K0.5Na0.5NbO3 (KNN) thin films grown on La0.67Sr0.33MnO3/SrTiO3 (001) substrates over the thickness range 20-80 nm using scanning probe microscopy. Kelvin probe force microscopy (KFM) and piezoresponse force microscopy were performed on pulsed-laser-deposition-deposited KNN thin films for studying the time evolution of trapped charges and polarized domains, respectively. The KFM data show that the magnitude and retention time of the surface potential are the maxima for 80 nm-thick film and reduce with the reduction in the film thickness. The charging and discharging of the samples reveal the easier and stronger electron trapping compared to hole trapping. This result further indicates the asymmetry between retention of the pulse-voltage-induced upward and downward domains. Furthermore, the time evolution of these ferroelectric nanodomains are found to obey stretched exponential behavior. The relaxation time (T) has been found to increase with increase in thickness; however, the corresponding stretched exponent (ß) is reduced. Moreover, the written domain can retain for more than 2300 min in KNN thin films. An in-depth understanding of domain relaxation dynamics in Pb-free KNN thin films can bridge a path for future high-density memory applications.