Activity-Based Sensing with a Metal-Directed Acyl Imidazole Strategy Reveals Cell Type-Dependent Pools of Labile Brain Copper

• DOI: 10.1021/jacs.0c05727
• Publication Date: 2020-08-20T10:15:05Z
• Authors: Sumin Lee; Clive Yik-Sham Chung; Pei Liu; Laura Craciun; Yuki Nishikawa; Kevin J. Bruemmer; Itaru Hamachi; Kaoru Saijo; Evan W. Miller; Christopher J. Chang
• Keywords: Copper deficiency; Cell type; Copper toxicity

Copper is a required nutrient for life and particularly important to the brain central nervous system. Indeed, copper redox activity essential maintaining normal physiological responses spanning neural signaling metabolism, but at same time misregulation associated with inflammation neurodegeneration. As such, chemical probes that can track dynamic changes in spatial resolution, especially loosely bound, labile forms, are valuable tools identify characterize its contributions healthy disease states. In this report, we present an activity-based sensing (ABS) strategy detection live cells preserves information by copper-dependent bioconjugation reaction. Specifically, designed copper-directed acyl imidazole dyes operate through copper-mediated activation of electrophiles subsequent labeling proximal proteins sites elevated provide permanent stain resists washing fixation. To showcase utility new ABS platform, sought pools three main cell types brain: neurons, astrocytes, microglia. Exposure each these physiologically relevant stimuli shows distinct pools. Neurons display translocation from somatic bodies peripheral processes upon activation, whereas astrocytes microglia exhibit global decreases increases intracellular pools, respectively, after exposure inflammatory stimuli. This work provides foundational on type-dependent homeostasis copper, metal brain, as well starting point design metals other stress analytes biology.