---
title: "Correlative Atomic Force Microscopy and Histology for Undecalcified Bone Microscale Mapping"
id: "biorxiv-6-microscale-characterization-of-undecalcified-bone-tissue-using-correlative"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-6-microscale-characterization-of-undecalcified-bone-tissue-using-correlative"
content_type: "clinical_feed_article"
specialty: "Radiology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.16.759704v1?rss=1"
published_at: "2026-10-22T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Correlative Atomic Force Microscopy and Histology for Undecalcified Bone Microscale Mapping
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-6-microscale-characterization-of-undecalcified-bone-tissue-using-correlative
- **Specialty:** [Radiology](https://medichelpline.com/clinical-feed/radiology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.16.759704v1?rss=1)
- **Published At:** 2026-10-22T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators developed an integrated workflow combining **atomic force microscopy** (AFM) with histology and immunofluorescence on adjacent cryosections of **undecalcified bone**. - The team used a tape-transfer mounting approach to preserve mineralized matrix and enable multimodal imaging on a single mouse femur section. - Data indicated that chemical decalcification substantially changes nanoscale surface topography and local mechanical properties compared with undecalcified tissue. - Applied to an aging cohort of female **C57BL/6J** mice aged 7–115 weeks, the method detected age-associated shifts in bone matrix structure and stiffness. - Authors reported the approach as broadly applicable to disease models that include cancer metastasis, osteoporosis, and osteoarthritis. - This report is a preprint; the authors noted no competing interests. Detailed instrument parameters and full procedural settings were not reported in the abstract or metadata.
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Nada Wahman 1 Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Nada%2BWahman%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Wahman%20N&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANada%2BWahman%2B) Young Hun Kim 2 Boston Children's Hospital, Boston, MA USA * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Young%2BHun%2BKim%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Kim%20YH&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AYoung%2BHun%2BKim%2B) Jahkwaun Budhai 1 Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jahkwaun%2BBudhai%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Budhai%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJahkwaun%2BBudhai%2B) Bikhyat Shrestha 1 Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Bikhyat%2BShrestha%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Shrestha%20B&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ABikhyat%2BShrestha%2B) Francesca Mazzoni 1 Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Francesca%2BMazzoni%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Mazzoni%20F&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AFrancesca%2BMazzoni%2B) Crystal Huang 1 Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Crystal%2BHuang%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Huang%20C&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ACrystal%2BHuang%2B) Ning Fan 1 Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ning%2BFan%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Fan%20N&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANing%2BFan%2B) Eric Chan 1 Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Eric%2BChan%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Chan%20E&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AEric%2BChan%2B) Eric Rosiek 1 Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Eric%2BRosiek%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Rosiek%20E&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AEric%2BRosiek%2B) Murray J Tipping 1 Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY USA; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Murray%2BJ%2BTipping%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Tipping%20MJ&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMurray%2BJ%2BTipping%2B) * [ORCID record for Murray J Tipping](http://orcid.org/0000-0001-5262-2723 "Open in new tab") * For correspondence: tippingm@mskcc.org * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.16.759704v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5894168/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.16.759704v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5894168/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.16.759704v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5894168/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.16.759704v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5894168/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.16.759704v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5894168/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Characterizing bone tissue in its mineralized state remains technically challenging. Conventional approaches typically compromise mechanical integrity through decalcification or lack the structural resolution necessary to capture microscale heterogeneity. Here we present an integrated workflow combining atomic force microscopy (AFM) with histological and immunofluorescence assays on adjacent undecalcified bone tissue cryosections. Using a tape-transfer mounting approach, we resolve mechanically and structurally distinct tissue types within a minimally processed single mouse femur section. Furthermore, we show that decalcification substantially alters nanoscale surface topography and local mechanical properties. Applied to an aging cohort of C57BL/6J female mice spanning 7 to 115 weeks, the proposed method detects age-associated changes in bone matrix structure and stiffness. The approach provides a practical methodology for spatially correlating nanomechanical properties with molecular markers in bone and other mineralized tissues, with broad applicability to disease models including cancer metastasis, osteoporosis, and osteoarthritis. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared National Institutes of Health, https://ror.org/01cwqze88, P30 CA008748 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-ND 4.0 International license](http://creativecommons.org/licenses/by-nd/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.16.759704v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/22/2026.10.16.759704.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.10.16.759704v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Microscale Characterization of Undecalcified Bone Tissue Using Correlative Atomic Force Microscopy and Histology Nada Wahman, Young Hun Kim, Jahkwaun Budhai, Bikhyat Shrestha, Francesca Mazzoni, Crystal Huang, Ning Fan, Eric Chan, Eric Rosiek, Murray J Tipping bioRxiv 2026.10.16.759704; doi: https://doi.org/10.64898/2026.10.16.759704 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Share This Article: Copy [![Twitter logo](https://www.biorxiv.org/sites/all/modules/highwire/highwire/images/twitter.png)](https://www.biorxiv.org/highwire_log/share/twitter?link=http%3A%2F%2Ftwitter.com%2Fshare%3Furl%3Dhttps%253A%2F%2Fwww.biorxiv.org%2Fcontent%2F10.64898%2F2026.10.16.759704v1%26text%3DMicroscale%2520Characterization%2520of%2520Undecalcified%2520Bone%2520Tissue%2520Using%2520Correlative%2520Atomic%2520Force%2520Microscopy%2520and%2520Histology "Share this on Twitter") [![Facebook logo](https://www.biorxiv.org/sites/all/modules/highwire/highwire/images/fb-blue.png)](https://www.biorxiv.org/highwire_log/share/facebook?link=http%3A%2F%2Fwww.facebook.com%2Fsharer.php%3Fu%3Dhttps%253A%2F%2Fwww.biorxiv.org%2Fcontent%2F10.64898%2F2026.10.16.759704v1%26t%3DMicroscale%2520Characterization%2520of%2520Undecalcified%2520Bone%2520Tissue%2520Using%2520Correlative%2520Atomic%2520Force%2520Microscopy%2520and%2520Histology "Share on Facebook") [![LinkedIn logo](https://www.biorxiv.org/sites/all/modules/highwire/highwire/i
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