One of the congenital flaws of metabolism, phenylketonuria (PKU), is known to be related to the self-assembly of toxic fibrillar aggregates of phenylalanine (Phe) in blood at elevated concentrations. Our experimental findings using L-phenylalanine (L-Phe) at millimolar concentration suggest the formation of fibrillar morphologies in the dry phase, which in the solution phase interact strongly with the model membrane composed of 1,2-diacyl-sn-glycerophosphocholine (LAPC) lipid, thereby decreasing the rigidity (or increasing the fluidity) of the membrane. The hydrophobic interaction, in addition to the electrostatic attraction of Phe with the model membrane, is found to be responsible for such phenomena. On the contrary, various microscopic observations reveal that such fibrillar morphologies of L-Phe are severely ruptured in the presence of its enantiomer D-phenylalanine (D-Phe), thereby converting the fibrillar morphologies into crushed flakes. Various biophysical studies, including the solvation dynamics experiment, suggest that this L-Phe in the presence of D-Phe, when interacting with the same model membrane, now reverts the rigidity of the membrane, i.e., increases the rigidity of the membrane, which was lost due to interaction with L-Phe exclusively. Fluorescence anisotropy measurements also support this reverse rigid character of the membrane in the presence of an enantiomeric mixture of amino acids. A comprehensive understanding of the interaction of Phe with the model membrane is further pursued at the single-molecular fluorescence detection level using fluorescence correlation spectroscopy (FCS) experiments. Therefore, our experimental conclusion interprets a linear correlation between increased permeability and enhanced fluidity of the membrane in the presence of L-Phe and certifies D-Phe as a therapeutic modulator of L-Phe fibrillar morphologies. Further, the study proposes that the rigidity of the membrane lost due to interaction with L-Phe was reinstatedin fact, increased in the presence of the enantiomeric mixture containing both D-and L-Phe.

The prolonged intake of the artificial sweetener aspartame is known to have deleterious effects. Our biophysical experimentations indicate that aspartame forms self-assembled fibrillar etiologies that affect the intrinsic integrity of...

The incorrect metabolic breakdown of the nonaromatic amino acid methionine (Met) leads to the disorder called hypermethioninemia via an unknown mechanism. To understand the molecular level pathogenesis of this disorder, we prepared a DMPC lipid membrane, the mimicking setup of the cell membrane, and explored the effect of the millimolar level of Met on it. We found that Met forms toxic fibrillar aggregates that disrupt the rigidity of the membrane bilayer, and increases the dynamic response of water molecules surrounding the membrane as well as the heterogeneity of the membrane. Such aggregates strongly deform red blood cells. This opens the requirement to consider therapeutic antagonists either to resist or to inhibit the toxic amyloid aggregates against hypermethioninemia. Moreover, such disrupting effect on membrane bilayer and cytotoxicity along with deformation effect on RBC by the cross amyloids of Met and Phenylalanine (Phe) was found to be most virulent. This exclusive observation of the enhanced virulent effect of the cross amyloids is expected to be an informative asset to explain the coexistence of two amyloid disorders.

In the present contribution, on the basis of a spectroscopic and microscopic investigation, the characterization and photophysics of various assemblies of oleic acid/oleate solution at three pH values, namely, 8.28, 9.72, and 11.77, were explored. The variation in the dynamic response of aqua molecules in and around the assemblies has been interrogated by a picoseconds solvation dynamics experiment using a timecorrelated single-photon counting setup employing coumarin-153 as a probe. On the one hand, the time-resolved fluorescence anisotropy measurement along with the fluorescence correlation spectroscopy experiment was executed to extract information regarding the comparison of the extent of the internal restricted confinement of these assemblies. On the other hand, an effort to investigate the cross-interaction between the self-assembled architectures of L-phenylalanine (L-Phe), responsible for phenylketonuria (PKU) disorder, and the oleic acid at the vesicle-forming pH established that the L-Phe fibrillar morphologies strongly alter the dynamic properties of the vesicle membrane formed by the oleic acid. Specifically, the interaction of the L-Phe assemblies with the oleic acid vesicle membrane is found to introduce the flexibility of the vesicle membrane and alter the hydration properties of the membrane. To track the fibril-induced alterations of the oleic acid vesicle properties, various spectroscopic and microscopic investigations were performed. The mutual reconciliation of the experimental outputs, therefore, portrays the state of the art, which accounts for the fibril-induced alterations of the properties of the oleic acid vesicle membrane, the mimicking setup of the cellular membrane, thereby informing us that alterations of such a property of the membrane should be taken into active consideration during the rational development of therapeutic modulators against disorders like PKU.

Gold nanoclusters (Au NCs) are an emerging class of fluorescent nanomaterials due to their fascinating chemical or physical properties and atomically precise structures; hence, they have been widely used in the field of biosensing and bioimaging. In this article, we demonstrate the green synthesis of orange, yellow, green, and cyan emitting Au NCs by core etching and ligand exchange methodology. Our investigation reveals that the chain length of the mercaptan acids, which are present on the surface of the Au NCs, controls the optical and electronic properties of the synthesized NCs. The steady-state and time-resolved spectroscopic data suggest that the emission properties of Au NCs mainly originate from the ligand to metal charge transfer (LMCT) transition. Alterations of the optical properties of these Au NCs can be proposed due to the difference in the core size of the Au NCs, which is strongly influenced by the surface-capping ligands. These NCs are highly biocompatible and nontoxic as evidenced by the cell viability and cellular uptake studies. By virtue of this, our as-synthesized NCs have been successfully used as excellent intracellular fluorescent imaging probes. Interestingly, fluorescence properties of Au NCs can efficiently probe the protein amyloids associated with several neurodegenerative diseases. To facilitate research in the field of amyloidosis, we have demonstrated fluorescence lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS) as two advanced tools to probe the aggregation of proteins and to monitor the physical interactions between proteins and NCs. It has been observed that the hydrophobicity of the NC surface can trigger the amyloid detection capability of Au NCs. Owing to these unique optical and attractive biological properties coupled with the imaging capability, these ultrasmall-sized Au NCs may enable in vivo detection of amyloids in the near future.