Anchoring-Detection Fluorescent Probe for Investigating Microcystin-LR-Induced Plasma Membrane Damage

Microcystin-LR (MC-LR), derived from cyanobacterial blooms, is a highly potent hepatotoxin that can enter the human body through ingestion, inhalation, and dermal absorption. Deciphering the toxic mechanism of MC-LR can provide insights into pathogenesis, which is valuable for ensuring drinking water safety and health. However, due to the lack of suitable in situ visualization tools, researchers have been unable to determine the plasma membrane damage process caused by MC-LR, including the tension, morphology, and permeability changes. With this research, we propose a rational strategy to develop a robust anchoring and specific recognition fluorescent probe, which can facilitate simultaneous fluorescence imaging of the plasma membrane and MC-LR. Using the probe, we observed the accumulation of MC-LR on the plasma membrane. More interestingly, fluorescence imaging using the unique anchoring-detection probe technique reveals a damage process of the plasma membrane of primary hepatocytes caused by MC-LR: during the damage process, the plasma membrane sequentially undergoes contraction, wrinkling, and ulceration, ultimately leading to the loss of membrane permeability regulation function, and the process is accompanied by severe nuclear collapse and nuclear envelope contraction.