Chain-controlled strategy for ratiometric evaluation of mitochondrial membrane potential in J-aggregation mechanism

Abstract

Ratiometric probes for mitochondrial membrane potential (∆Ψm) are critical tools for the precise visualization of ∆Ψm. Cyanine dyes with red-shifted J-aggregates are potential for ratiometric detection of ∆Ψm, but are rarely employed as probes for ∆Ψm owing to the deficiency of design strategy. Herein, we proposed a side-chain regulation strategy to construct ratiometric probes for ∆Ψm. The cyanine dye with too short chain exhibited lower sensitivity to ∆Ψm, because partial the probe molecules dispersed in mitochondrial matrix to give monomer emission. The cyanine dye with too long chain cannot be used either, because the long chain hampered the intermolecular stack to form J-aggregates. Only cyanine dye with proper chain length was gathered in mitochondrial inner membrane to efficiently form red-shifted J-aggregates. Based on this strategy, a robust probe J-mito was successfully constructed for ratiometric visualization of ∆Ψm. J-mito formed J-aggregates with deep-red emission in mitochondria with high ∆Ψm, which switched into green-emissive monomer after the loss of ∆Ψm. With the probe, the reversible variation in ∆Ψm upon the addition and removal of CCCP has been successfully monitored. The decreased level of ∆Ψm under oxidative stress, high and low temperature, and high glucose and palmitic acid treatment was also successfully revealed.