---
title: "Fluid Shear Stress Drives Mechanoadaptive Fibroblast Remodeling and Early Fibrogenesis Signatures"
id: "biorxiv-17-ultrastructural-and-proteomic-signatures-of-mechanoadaptive-fibroblast"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-17-ultrastructural-and-proteomic-signatures-of-mechanoadaptive-fibroblast"
content_type: "clinical_feed_article"
specialty: "Gastroenterology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.13.751238v1?rss=1"
published_at: "2026-09-18T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Fluid Shear Stress Drives Mechanoadaptive Fibroblast Remodeling and Early Fibrogenesis Signatures
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-17-ultrastructural-and-proteomic-signatures-of-mechanoadaptive-fibroblast
- **Specialty:** [Gastroenterology](https://medichelpline.com/clinical-feed/gastroenterology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.13.751238v1?rss=1)
- **Published At:** 2026-09-18T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Engineered shear platforms—a microfluidic gut-on-a-chip and a mesofluidic rotary shaker—were used to test how sustained **fluid shear stress** affects primary normal human intestinal fibroblasts. - Sustained shear alone was reported as necessary and sufficient to induce an irreversible, profibrotic phenotypic switch in these fibroblasts. - Across both devices, fibroblasts from small and large intestine reproducibly self-organized into **three-dimensional (3D) multicellular aggregates** within 72 hours, indicating the response depends on mechanical dose rather than device geometry. - The aggregated cells acquired robust **α-smooth muscle actin (α-SMA)** expression and exhibited aligned stress fibers, in contrast to the α-SMA–negative parental population. - Scanning electron microscopy (SEM) resolved densely packed cellular microarchitecture embedded in a **microfibrillar extracellular network**. - Serial block-face 3D electron microscopy identified expansive intercellular spaces, stochastic fibrillar extrusions, and electron-dense cytoplasmic material at cell boundaries in the aggregates. - Proteomic profiling showed enrichment of **core matrisome components**, including multiple collagen subtypes and **matrix metalloproteinases (MMPs)**, consistent with extracellular matrix remodeling. - Authors conclude that **fluid shear stress** is a platform-independent mechanical trigger for a fibroblast-to-mechanoadaptive transition and propose microphysiological shear platforms as tractable tools to model and target early fibrogenesis in inflammatory bowel disease (IBD). - The study declares no competing interests and lists multiple funders, including NIH, Kenneth Rainin Foundation, Crohn's and Colitis Foundation, and Korean funding sources.
## Clinical Analysis & Structured Key Points
Ultrastructural and Proteomic Signatures of Mechanoadaptive Fibroblast Remodeling across Microphysiological and Mesoscale Shear Platforms | bioRxiv Skip to main content New Results Ultrastructural and Proteomic Signatures of Mechanoadaptive Fibroblast Remodeling across Microphysiological and Mesoscale Shear Platforms View ORCID Profile Soyoun Min , View ORCID Profile Hyeon-Su Jin , View ORCID Profile Grahame Kidd , View ORCID Profile Emily Benson , View ORCID Profile Dong-Woo Lee , View ORCID Profile Hyun Jung Kim doi: https://doi.org/10.64898/2026.09.13.751238 Soyoun Min 1 Cleveland Clinic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Soyoun Min Hyeon-Su Jin 2 Yonsei University Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Hyeon-Su Jin Grahame Kidd 1 Cleveland Clinic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Grahame Kidd Emily Benson 1 Cleveland Clinic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Emily Benson Dong-Woo Lee 2 Yonsei University Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Dong-Woo Lee Hyun Jung Kim 1 Cleveland Clinic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Hyun Jung Kim For correspondence: biomelab.2022{at}gmail.com Abstract Info/History Metrics Supplementary material Preview PDF Abstract Mechanobiological cues in the tissue microenvironment increasingly drive pathological fibroblast activation in inflammatory bowel disease (IBD), yet engineered platforms modeling this transition remain limited. Here, a microfluidic gut-on-a-chip microphysiological system and a mesofluidic rotary shaker are used to demonstrate that sustained fluid shear stress alone is necessary and sufficient to drive an irreversible, profibrotic phenotypic switch in primary normal human intestinal fibroblasts. Across both platforms, normal fibroblasts from small and large intestine reproducibly self-organize into three-dimensional (3D) multicellular aggregates within 72 h, independent of shear delivery format, indicating that the transition is governed by mechanical dose rather than device geometry. The resulting aggregates acquire robust α-smooth muscle actin (α-SMA) expression with aligned stress fibers, contrasting with the α-SMA-negative parental population. Scanning electron microscopy (SEM) resolves densely packed cellular microarchitecture embedded in a microfibrillar extracellular network, while ultrastructural serial block-face 3D EM reveals expansive intercellular spaces, stochastic fibrillar extrusions, and electron-dense cytoplasmic material at cell boundaries. Proteomic profiling confirms enrichment of core matrisome components, including collagen subtypes and matrix metalloproteinases. Together, these results establish fluid shear stress as a platform-independent, sufficient mechanical trigger for fibroblast-to-mechanoadaptive transition, positioning microphysiological shear platforms as tractable tools for modeling and targeting early fibrogenesis in IBD. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared NIH NCI IMAT program , 1R33CA286797 Kenneth Rainin Foundation, https://ror.org/00dkwrz68 , Innovator Award Crohn's and Colitis Foundation, https://ror.org/05f2xbq60 , Senior Research Award Bio-industrial Technology Development Program from the Ministry of Trade, Industry & Energy Korea , 20018770 National Research Foundation of Korea grant funded by the Korean government , RS-2025-02215093 Clinical and Translational Science Collaborative of Northern Ohio funded by the NIH NCATS , UM1TR004528 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Posted September 18, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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Share Ultrastructural and Proteomic Signatures of Mechanoadaptive Fibroblast Remodeling across Microphysiological and Mesoscale Shear Platforms Soyoun Min , Hyeon-Su Jin , Grahame Kidd , Emily Benson , Dong-Woo Lee , Hyun Jung Kim bioRxiv 2026.09.13.751238; doi: https://doi.org/10.64898/2026.09.13.751238 Share This Article: Copy Citation Tools Ultrastructural and Proteomic Signatures of Mechanoadaptive Fibroblast Remodeling across Microphysiological and Mesoscale Shear Platforms Soyoun Min , Hyeon-Su Jin , Grahame Kidd , Emily Benson , Dong-Woo Lee , Hyun Jung Kim bioRxiv 2026.09.13.751238; doi: https://doi.org/10.64898/2026.09.13.751238 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8010) Biochemistry (18733) Bioengineering (14878) Bioinformatics (44394) Biophysics (22589) Cancer Biology (19717) Cell Biology (26897) Clinical Trials (138) Developmental Biology (13964) Ecology (21005) Epidemiology (2067) Evolutionary Biology (25436) Genetics (16162) Genomics (23498) Immunology (18693) Microbiology (42451) Molecular Biology (18056) Neuroscience (93420) Paleontology (700) Pathology (2977) Pharmacology and Toxicology (5093) Physiology (8111) Plant Biology (15998) Scientific Communication and Education (2095) Synthetic Biology (4559) Systems Biology (10233) Zoology (2390)
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