PT - JOURNAL ARTICLE AU - Xiaoyu Shi AU - Qi Li AU - Zhipeng Dai AU - Arthur A. Tran AU - Siyu Feng AU - Alejandro D. Ramirez AU - Zixi Lin AU - Xiaomeng Wang AU - Tracy T. Chow AU - Jiapei Chen AU - Dhivya Kumar AU - Andrew R. McColloch AU - Jeremy F. Reiter AU - Eric J. Huang AU - Ian B. Seiple AU - Bo Huang TI - Label-retention expansion microscopy AID - 10.1101/687954 DP - 2021 Jan 01 TA - bioRxiv PG - 687954 4099 - http://biorxiv.org/content/early/2021/03/04/687954.short 4100 - http://biorxiv.org/content/early/2021/03/04/687954.full AB - Expansion microscopy (ExM) increases the effective resolving power of any microscope by expanding the sample with swellable hydrogel. Since its invention, ExM has been successfully applied to a wide range of cell, tissue and animal samples. Still, fluorescence signal loss during polymerization and digestion limits molecular-scale imaging using ExM. Here we report the development of label-retention ExM (LR-ExM) with a set of trifunctional anchors that not only prevent signal loss but also enable high-efficiency labeling using SNAP and CLIP tags. We have demonstrated multicolor LR-ExM for a variety of subcellular structures. Combining LR-ExM with super-resolution Stochastic Optical Reconstruction Microscopy (STORM), we have achieved molecular resolution in the visualization of polyhedral lattice of clathrin-coated pits in situ.Competing Interest StatementThe authors have declared no competing interest.