---
title: "Hyaluronan Surface Architecture Controls Colorectal Cancer Stage and Extracellular Vesicle Communi"
id: "biorxiv-7-hyaluronan-surface-architecture-dictates-colorectal-cancer-progression-and"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-7-hyaluronan-surface-architecture-dictates-colorectal-cancer-progression-and"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.16.751988v1?rss=1"
published_at: "2026-09-22T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Hyaluronan Surface Architecture Controls Colorectal Cancer Stage and Extracellular Vesicle Communi
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-7-hyaluronan-surface-architecture-dictates-colorectal-cancer-progression-and
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.16.751988v1?rss=1)
- **Published At:** 2026-09-22T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study maps nanoscale surface organization of **hyaluronan (HA)** on colorectal cancer (CRC) cells and their **extracellular vesicles (EVs)** across Dukes' stages using single-molecule force spectroscopy. - **HA density** rises with advancing Dukes' stage in both cell surfaces and EVs, but chain organization diverges between the two compartments. - Cell-surface HA becomes progressively **fragmented** with stage, while EVs remain enriched in **short HA chains** at all stages, implying selective incorporation of HA into EVs during biogenesis rather than simple inheritance from parent cells. - Both cells and EVs show stage-associated **softening**, and enzymatic removal of HA reverses this softening, linking HA architecture to mechanical properties. - Coarse-grained membrane simulations indicate that **HA chain length** and **surface density** differentially regulate membrane wrapping: chain length mainly alters wrapping kinetics, while surface density controls the final extent of wrapping. - The simulated and experimental findings together provide a mechanistic explanation for observed differences in EV uptake by recipient cells. - Reprogramming stage D CRC cells with exogenous high-molecular-weight HA reduced EV surface HA density, increased vesicle stiffness, slowed cell migration, and suppressed EV uptake, showing that the HA surface signature is experimentally reversible. - The authors conclude that **HA surface architecture** is a stage-encoded, reversible determinant of CRC progression and EV-mediated communication. The work is reported as a preprint and has not been peer reviewed.
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DEBASHISH PAUL 1 Shiv Nadar Institution of Eminence; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=DEBASHISH%2BPAUL%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=PAUL%20D&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ADEBASHISH%2BPAUL%2B) * [ORCID record for DEBASHISH PAUL](http://orcid.org/0000-0002-6764-5052 "Open in new tab") Neha Mathur 2 Indian Institute of Science Education and Research Mohali; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Neha%2BMathur%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Mathur%20N&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANeha%2BMathur%2B) Tanya Agrawal 3 Shiv Nadar Institution of eminence; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Tanya%2BAgrawal%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Agrawal%20T&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ATanya%2BAgrawal%2B) * [ORCID record for Tanya Agrawal](http://orcid.org/0009-0009-4618-0717 "Open in new tab") Sunita Saha 4 Indian Institute of Technology Bhilai * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Sunita%2BSaha%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Saha%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASunita%2BSaha%2B) Natasha Natasha 1 Shiv Nadar Institution of Eminence; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Natasha%2BNatasha%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Natasha%20N&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANatasha%2BNatasha%2B) Suchetan Pal 4 Indian Institute of Technology Bhilai * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Suchetan%2BPal%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Pal%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASuchetan%2BPal%2B) * [ORCID record for Suchetan Pal](http://orcid.org/0000-0002-6323-7502 "Open in new tab") Anil Kumar Dasanna 2 Indian Institute of Science Education and Research Mohali; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Anil%2BKumar%2BDasanna%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Dasanna%20AK&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAnil%2BKumar%2BDasanna%2B) Tatini Rakshit 1 Shiv Nadar Institution of Eminence; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Tatini%2BRakshit%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Rakshit%20T&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ATatini%2BRakshit%2B) * For correspondence: tatini.rakshit@snu.edu.in * [Abstract](https://www.biorxiv.org/content/10.64898/2026.09.16.751988v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5801756/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.09.16.751988v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5801756/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.09.16.751988v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5801756/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.09.16.751988v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5801756/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Hyaluronan (HA) is a principal component of the tumor glycocalyx in colorectal cancer (CRC). However, how the disease progression is linked to HA abundance and its nanoscale organization remains unclear. Single-molecule measurements of surface glycans on cell membranes and extracellular vesicles (EVs) have not yet been correlated. In this work, using single-molecule force spectroscopy, we mapped HA density and chain length on CRC cells and their EVs across Dukes' stages. HA density increased with stage in both compartments, but their organization diverged. Cell-surface HA became progressively fragmented, whereas EVs remained enriched in short HA chains at every stage. EVs, therefore, appear to select HA during formation rather than inherit it from the parent cell. This divergence had mechanical consequences. Both cells and EVs softened with stage, and removing HA reversed this softening. In addition, coarse-grained membrane simulations revealed that both HA chain length and surface density regulate membrane wrapping, with chain length primarily influencing wrapping kinetics and surface density affecting the final wrapping extent. These findings provide a physical basis for the differences we observed in EV uptake. Reprogramming stage D cells with exogenous high-molecular-weight HA reversed this signature, lowering EV surface HA density, stiffening the vesicles, slowing migration, and suppressing EV uptake by recipient cells. These findings establish HA surface architecture as a stage-encoded and experimentally reversible determinant of CRC progression. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared Science and Engineering Research Board, CRG/2023/003029, ANRF/ARG/2025/005072/LS Shiv Nadar Foundation, SNF season 3 collaboration grant (COLLAB0011) 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-NC-ND 4.0 International license](http://creativecommons.org/licenses/by-nc-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/10.64898/2026.09.16.751988v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/09/22/2026.09.16.751988.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Hyaluronan Surface Architecture Dictates Colorectal Cancer Progression and Extracellular Vesicle Communication DEBASHISH PAUL, Neha Mathur, Tanya Agrawal, Sunita Saha, Natasha Natasha, Suchetan Pal, Anil Kumar Dasanna, Tatini Rakshit bioRxiv 2026.09.16.751988; doi: https://doi.org/10.64898/2026.09.16.751988 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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