MechanoMaST - a multimodal pipeline for spatially registering mechanical and transcriptomic tissue data
- 1Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany
Abstract
Spatial-omics workflows enable spatially-resolved molecular analysis within tissues. Despite the prognostic value of tissue stiffness, these approaches have not yet incorporated direct, absolute mechanical measurements. This omission reflects several challenges, including sample requirements, low throughput, and the need for specialized equipment and complex data registration. Here, we introduce MechanoMaST (mechanics mapped to spatial transcriptomics), a workflow that combines absolute mechanical measurements with spatial-omics. It pairs atomic force microscopy-based nanoindentation stiffness maps with spatial transcriptomics maps from adjacent tissue cryosections. The two modalities are computationally co-registered to enable spatial correlation at 100 m resolution with a sub-10 m mean accuracy, providing ground-truth mechanical data directly linked to spatial gene expression. We demonstrate MechanoMaST in human colorectal cancer liver metastasis, generating a spatial resource from 10 patients and revealing a five-gene stiffness signature. MechanoMaST is readily adaptable to other tissues across development and disease, and extendable to additional spatial-omics modalities.
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BibTeX
@misc{decker2026mechanomast,
title = {{MechanoMaST - a multimodal pipeline for spatially registering mechanical and transcriptomic tissue data}},
author = {L. Decker and D. Olisov and N. Schleussner and H. Wiethoff and T. Schmidt and H. Nienhueser and T. M. Pausch and J. O. Korbel and A. Diz-Munoz},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.29.747727},
url = {https://www.biorxiv.org/content/10.64898/2026.08.29.747727v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - MechanoMaST - a multimodal pipeline for spatially registering mechanical and transcriptomic tissue data
AU - L. Decker
AU - D. Olisov
AU - N. Schleussner
AU - H. Wiethoff
AU - T. Schmidt
AU - H. Nienhueser
AU - T. M. Pausch
AU - J. O. Korbel
AU - A. Diz-Munoz
PY - 2026
DA - 2026/08/29
PB - bioRxiv
DO - 10.64898/2026.08.29.747727
UR - https://www.biorxiv.org/content/10.64898/2026.08.29.747727v1
AB - Spatial-omics workflows enable spatially-resolved molecular analysis within tissues. Despite the prognostic value of tissue stiffness, these approaches have not yet incorporated direct, absolute mechanical measurements. This omission reflects several challenges, including sample requirements, low throughput, and the need for specialized equipment and complex data registration. Here, we introduce MechanoMaST (mechanics mapped to spatial transcriptomics), a workflow that combines absolute mechanical measurements with spatial-omics. It pairs atomic force microscopy-based nanoindentation stiffness maps with spatial transcriptomics maps from adjacent tissue cryosections. The two modalities are computationally co-registered to enable spatial correlation at 100 m resolution with a sub-10 m mean accuracy, providing ground-truth mechanical data directly linked to spatial gene expression. We demonstrate MechanoMaST in human colorectal cancer liver metastasis, generating a spatial resource from 10 patients and revealing a five-gene stiffness signature. MechanoMaST is readily adaptable to other tissues across development and disease, and extendable to additional spatial-omics modalities.
ER -