Hex-MASP for mapping the whole-tissue spatial proteome and the intrabrain distribution of monoclonal antibodies.

Authors

Shihan Huo, Min Ma, Shuo Qian, Ming Zhang, Jie Pu, Xiaoyu Zhu, Sailee Rasam, Tara Barone, Robert Plunkett, Chi Zhou, Jun Qu

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 36. Pages e2532946123. Sep 08, 2026. Epub Sep 03, 2026.

Abstract

Whole-tissue level spatial proteomics provides critical insights into region-specific biological regulations but remains challenging. Previously, we introduced the micro-scaffold assisted spatial proteomics (MASP) concept for whole-tissue mapping. However, this prototype required substantial development in spatial resolution, practicality, and throughput for practical application. Here we present a next-generation MASP technique (hex-MASP) featuring i) a new design of hexagonal-micro-wells fabricated with optimized projection micro-stereolithography 3D-printing, achieving high spatial resolution, sampling robustness, and mechanical strength for reproducibly compartmentalizing even tough tissues; ii) enhanced throughput/effectiveness in sample preparation and LC-MS analysis with high quantitative quality. Applied to mouse brain, hex-MASP achieved in-depth, whole-tissue mapping for >6,000 proteins in mouse brains, with high spatial accuracy and excellent data quality. The substantially improved resolution revealed critical regional details across the entire brain, that were not previously captured, enabling precise depiction of protein distribution heterogeneity. This technique enabled the identification of many unreported regionally enriched proteins across brain structures. We further applied hex-MASP to investigate the intrabrain distribution of intracerebroventricularly dosed antibody therapeutics and related proteins, which enabled whole-tissue mapping of protein drugs revealed insights into antibody brain penetration and distribution. Hex-MASP represents a robust, scalable platform for whole-tissue spatial proteomics.

PMID:
42691083
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.

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