A π-conjugated porous organic polymer (BCzBz) was fabricated employing N,N'-bicarbazole and benzothiadiazole as molecular building units exhibiting broad visible light absorption. The photostable, water-dispersible, and cytocompatible BCzBz was demonstrated as...

Small strategic perturbations of the molecular structures impart significant variation in the evolution dynamics and properties of supramolecular self-assembled architectures. However, probing the in situ evolution dynamics of molecular assembly remains a challenge. Herein, we unraveled the real-time, early stage environment-sensitive dynamic molecular self-assembly processes and stimuli-induced reversible morphological transformation between supramolecular fibers and spherical nanoaggregates of alkyl chain-substituted phenanthroimidazole-based luminogen (BPIB1) through fluorescence lifetime imaging microscopy (FLIM). The presence of an octyl chain and basic nitrogen centers in BPIB1 led to a distinct self-assembly pattern. The gradual progression in the fluorescence lifetime provides a unique strategy for elucidating the dynamics of the self-assembly process leading to distinct nano/microarchitectures. Among the varied self-assembled structures, the smaller-sized (diameter ∼ 20–30 nm), highly photostable, water-dispersible, and biocompatible fluorescent nanoaggregates of BPIB1 were employed for tracking the dynamics of lipid droplets in live cells and a model organism, C. elegans, using fluorescence correlation spectroscopy and FLIM. Thus, a combined microscopic and spectroscopic approach demonstrated in the present study opens up new avenues to explore the formation pathways of diverse molecular aggregates and their use to decipher complex organelle dynamics.

A judicious structural modification of molecular building units imparts significant variation in the evolution dynamics of supramolecular self-assembled architectures and their functional properties. The incorporation of alkyl chains into the rigid and π-conjugated molecular backbone not only directs the self-assembly but also enhances the hydrophobicity of the probe, facilitating specific interactions with hydrophobic organelle like lipid droplets (LDs). Such a fluorescent molecular probe is ideally suited for elucidation of complex self-assembly processes and to decipher the intracellular dynamics of LDs. Invoking the concept, the main skeleton of 1,4-bis(1H-phenanthro[9,10-d]imidazol-2-yl)benzene abbreviated as BPIB, was functionalized with a varying number of octyl chains to obtain BPIB1 and BPIB2. The alkyl chains were crucial to circumvent the π-π stacking leading to the strong fluorescence in aggregates and solid-state. Contrary to BPIB and BPIB2, intermolecular interactions-driven spontaneous self-association of BPIB1 having an amine nitrogen center and a long alkyl chain resulted in a stimuli-responsive fluorescent organogel. We deciphered the reversible morphological transformation between supramolecular fibers and spherical nanoaggregates using fluorescence lifetime imaging microscopy. The gradual progression in the fluorescence lifetime provides a unique strategy for exploring the dynamics of the self-assembly process. Furthermore, BPIB1 was found to be a specific marker for LDs in multiple cell lines. The fluorescence correlation spectroscopy revealed the microenvironments near LDs. Highly photostable BPIB1 was employed for the real-time tracking of the LDs dynamics in live cells. Thus, a combined microscopic and spectroscopic approach demonstrated in the present study opens up new avenues for further exploration of intriguing molecular aggregation and intracellular dynamics.

Chromatin remodelling complexes are multi-subunit assemblies, each containing a catalytic ATPase and translocase that is capable of mobilizing nucleosomes to alter the chromatin structure. SWI/SNF remodelling complexes with higher DNA translocation efficiency evict histones or slide the nucleosomes away from each other making DNA accessible for transcription and repair machinery. Chromatin remodelling at the promoter of stress-responsive genes by SWI/SNF becomes necessary during the heat and proteotoxic stress. While the involvement of SWI/SNF in transcription of stress-responsive genes has been studied extensively, the regulation of proteostasis by SWI/SNF is not well understood. This study demonstrates critical functions of SWI/SNF in response to cadmium-induced proteotoxic stress. Deletion of either ATPasetranslocase subunit of SWI/SNF complex (Swi2/Snf2) or a regulatory subunit Swi3 abrogates the clearance of cadmium-induced protein aggregates. Our results suggest that Snf2 and Swi3 regulate the protein folding in endoplasmic reticulum (ER) that reduces the chances of forming unfolded protein aggregates under the proteotoxic stress of cadmium. The Ire1-mediated unfolded protein response (UPR) maintains ER homeostasis by upregulating the expression of chaperones and ER-associated degradation (ERAD) components. We found that Snf2 maintains normal oxidative environment essential for Ire1 activity. Deletion of SNF2 reduced the Ire1 activity and UPR, indicating involvement of Snf2 in Ire1-mediated ER proteostasis. Together, these findings suggest that SWI/SNF complex regulates ER homeostasis and protein folding crucial for tolerating proteotoxic stress.

No abstract