Report Three-dimensional multi-color optical nanoscopy at sub-10-nm resolution based on small-molecule organic probes

Achieving nanometer-scale resolution remains challenging in expansion microscopy due to photon loss. To address this concern, here we develop a multi-color expansion stimulated emission depletion technique based on small-molecule probes to realize high labeling density and intensity. Our method substantially lowers the barrier to visualizing diverse intracellular proteins and their interactions in three dimensions. It enables us to achieve sub-10-nm resolution in structures such as microfilaments, lysosomes, and mitochondria, providing new insights into cell biology.

Automated summary

In this study, a multi-color expansion stimulated emission depletion technique based on small-molecule probes is developed to achieve high labeling density and intensity, addressing the challenge of nanometer-scale resolution in expansion microscopy. The method enables sub-10-nm resolution imaging of intracellular proteins and their interactions in structures like microfilaments, lysosomes, and mitochondria, offering new insights into cell biology.