PT  - JOURNAL ARTICLE
AU  - Xavier Rovira-Clave
AU  - Sizun Jiang
AU  - Yunhao Bai
AU  - Graham Barlow
AU  - Salil Bhate
AU  - Ahmet F. Coskun
AU  - Guojun Han
AU  - Bokai Zhu
AU  - Chin-Min Kimmy Ho
AU  - Chuck Hitzman
AU  - Shih-Yu Chen
AU  - Felice-Alessio Bava
AU  - Garry P. Nolan
TI  - Subcellular localization of drug distribution by super-resolution ion beam imaging
AID  - 10.1101/557603
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 557603
4099  - http://biorxiv.org/content/early/2019/02/22/557603.short
4100  - http://biorxiv.org/content/early/2019/02/22/557603.full
AB  - Technologies that visualize multiple biomolecules at the nanometer scale in cells will enable deeper understanding of biological processes that proceed at the molecular scale. Current fluorescence-based methods for microscopy are constrained by a combination of spatial resolution limitations, limited parameters per experiment, and detector systems for the wide variety of biomolecules found in cells. We present here super-resolution ion beam imaging (srIBI), a secondary ion mass spectrometry approach capable of high-parameter imaging in 3D of targeted biological entities and exogenously added small molecules. Uniquely, the atomic constituents of the biomolecules themselves can often be used in our system as the “tag”. We visualized the subcellular localization of the chemotherapy drug cisplatin simultaneously with localization of five other nuclear structures, with further carbon elemental mapping and secondary electron visualization, down to ∼30 nm lateral resolution. Cisplatin was preferentially enriched in nuclear speckles and excluded from closed-chromatin regions, indicative of a role for cisplatin in active regions of chromatin. These data highlight how multiplexed super-resolution techniques, such as srIBI, will enable studies of biomolecule distributions in biologically relevant subcellular microenvironments.One Sentence Summary Three-dimensional multiplexed mass spectrometry-based imaging revealed the subcellular localization of proteins and small molecules at super-resolution.