Formation of membrane-less organelles by self-assembly of disordered proteins can be triggered by external stimuli such as pH, salt, or temperature. These organelles, called biomolecular condensates, have traditionally been classified as liquids, gels, or solids with limited subclasses. Here, the authors show that a thermal trigger can lead to formation of at least two distinct liquid condensed phases of the fused in sarcoma low complexity (FUS LC) domain. Forming FUS LC condensates directly at low temperature leads to formation of metastable, kinetically trapped condensates that show arrested coalescence, escape from which to untrapped condensates can be achieved via thermal annealing. Using experimental and computational approaches, the authors find that molecular structure of interfacial FUS LC in kinetically trapped condensates is distinct (more đˇ-sheet like) compared to untrapped FUS LC condensates. Moreover, molecular motion within kinetically trapped condensates is substantially slower compared to that in untrapped condensates thereby demonstrating two unique liquid FUS condensates. Controlling condensate thermodynamic state, stability, and structure with a simple thermal switch may contribute to pathological protein aggregate stability and provides a facile method to trigger condensate mixing for biotechnology applications.
Protein condensation into liquid-like structures is critical for cellular compartmentalization, RNA processing, and stress response. Research on protein condensation has primarily focused on membraneless organelles in the absence of lipids. However, the cellular cytoplasm is full of lipid interfaces, yet comparatively little is known about how lipids affect protein condensation. Here, we show that nonspecific interactions between lipids and the disordered fused in sarcoma low-complexity (FUS LC) domain strongly affect protein condensation. In the presence of anionic lipids, FUS LC formed lipid-protein clusters at concentrations more than 30-fold lower than required for pure FUS LC. Lipid-triggered FUS LC clusters showed less dynamic protein organization than canonical, lipid-free FUS LC condensates. Lastly, we found that phosphatidylserine membranes promoted FUS LC condensates having β sheet structures, while phosphatidylglycerol membranes initiated unstructured condensates. Our results show that lipids strongly influence FUS LC condensation, suggesting that protein-lipid interactions modulate condensate formation in cells.
A luminescent hybrid gel was prepared by incorporating organic ligand capped CdSe quantum dots (QDs) into a steroid-dimer derived organogel. Photophysical measurements and electron microscopy studies allowed us to understand the nature of the hybrid. Detailed analysis of the excited state dynamics of the hybrid was carried out using a kinetic decay model. The luminescence of the QDs in the hybrid was unaltered by taking it through a gel-sol-gel cycle induced by thermal stimuli. We believe that the results obtained herein provide a route to develop a thermoresponsive device for practical applications, because of the spatial assembly between soft organic scaffolds and colloidal QDs.
Biomolecular condensates, protein-rich and dynamic membrane-less organelles, play critical roles in a range of subcellular processes, including membrane trafficking and transcriptional regulation. However, aberrant phase transitions of intrinsically disordered proteins in biomolecular condensates can lead to the formation of irreversible fibrils and aggregates that are linked to neurodegenerative diseases. Despite the implications, the interactions underlying such transitions remain obscure. Here we investigate the role of hydrophobic interactions by studying the low-complexity domain of the disordered âfused in sarcomaâ (FUS) protein at the air/water interface. Using surface-specific microscopic and spectroscopic techniques, we find that a hydrophobic interface drives fibril formation and molecular ordering of FUS, resulting in solid-like film formation. This phase transition occurs at 600-fold lower FUS concentration than required for the canonical FUS low-complexity liquid droplet formation in bulk. These observations highlight the importance of hydrophobic effects for protein phase separation and suggest that interfacial properties drive distinct protein phase-separated structures.
A one step, in situ, room temperature synthesis of yellow luminescent CdSe QDs was achieved in a metallohydrogel derived from a facially amphiphilic bile salt, resulting in a QD-gel hybrid. An ordered self-assembly and homogeneous distribution of the CdSe QDs in the hydrogel network was observed from optical and electron micrographs. The different excited state behavior of the CdSe QDs in the hybrid was revealed for the first time using time resolved spectroscopy. We also describe the successful isolation of the photoluminescent CdSe QDs from the gel followed by their re-dispersion in an organic solvent using suitable capping ligands.
We have described a strategy towards integrating photoluminescent semiconductor nanoparticles into a bio-surfactant derived organogel. A facially amphiphilic bile thiol was used for capping CdS nanoparticles (NPs) which were embedded in a bile acid derived new organogelator in order to furnish a soft hybrid material. The presence of CdS NPs in a well-ordered 1D array on the organogel network was confirmed using microscopic techniques. Photophysical studies of the gel-NP hybrid revealed resolved excitation and emission characteristics. Time resolved spectroscopic studies showed that the average lifetime value of the CdS NPs increased in the gel state compared to the sol phase. A kinetic model was utilized to obtain quantitative information about the different decay pathways of the photoexcited NPs in the sol and gel states.
We have described here an efficient method to disperse hydrophobic CdSe quantum dots (QDs) in an aqueous phase using cetyltrimethylammonium bromide (CTAB) micelles without any surface ligand exchange. The water soluble QDs were then embedded in 3D self assembled fibrillar networks (SAFINs) of a hydrogel showing homogeneous dispersibility as evidenced from optical and electron microscopic techniques. The photophysical studies of the hydrogel-QD composite are reported for the first time. These composite materials may have potential applications in biology, optoelectronics, sensors, non-linear optics and materials science.
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