Abstract
Formation and accumulation of liquid droplets (LDs) represent a vital sign for homeostatic imbalance of pathological proteins or membranous organelles. However, the specific interactions and disease-leading mechanisms remain obscure. Here, we developed a series of BODIPY-based fluorogenic probes (PsBDP) that exhibit polarity-dependent fluorescence intensity and lifetime responses to determine microenvironmental polarity changes during LDs formation and accumulation. Through TD-DFT calculations, we reveal that rationally regulating the valence shells excitation form of compounds can improve their polarity sensitivity. In live cells, we find that mitochondrial membrane potential (MMP) depolarization induced by drugs promote LDs formation and accumulation. Interestingly, overexpression of pathological proteins in neurodegenerative diseases also accelerates LDs accumulation via MMP depolarization. Furthermore, through fluorescence lifetime imaging (FLIM), we observed a decreasing trend of LDs polarity as they grow mature. In summary, PsBDP provide a imaging toolset to quantitatively study the interactions between LDs accumulation and cellular dysfunction, serving to potentially benefit screening of LD modulators for disease intervention.
Published Version
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