---
title: "AFM Force-to-Signal Assay Reveals Glypican-1 and TRP Channel Roles in Endothelial Mechanotransduct"
id: "pubmed-42804384"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42804384"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42804384/"
doi: "10.1152/ajpheart.90228.2026"
published_at: "2026-09-28T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# AFM Force-to-Signal Assay Reveals Glypican-1 and TRP Channel Roles in Endothelial Mechanotransduct
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42804384
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42804384/)
- **DOI:** [10.1152/ajpheart.90228.2026](https://doi.org/10.1152%2Fajpheart.90228.2026)
- **Published At:** 2026-09-28T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The endothelial surface glycocalyx (ESG) is a carbohydrate-rich layer on endothelial cells composed of glycoproteins, proteoglycans, and glycosaminoglycans that transduces mechanical cues like shear stress into biochemical signals. - Impaired ESG mechanosignaling is associated with cardiovascular complications such as diabetes, stroke, sepsis, and atherosclerosis via reduced **nitric oxide (NO)** production. - The receptor-level mechanisms linking ESG mechanics to downstream NO signaling have been unclear. - The authors developed an atomic force microscopy (AFM) force-to-signal assay that applies controlled, receptor-targeted mechanical inputs (pico- to nano-newton range) to single live endothelial cells while recording **NO** production in real time via fluorescence. - The assay was used on mouse brain endothelial cells to pull on specific ESG components and simultaneously measure NO output, allowing direct mapping from mechanical input at a molecular receptor to downstream biochemical signal at single-cell resolution. - Key findings: **heparan sulfate (HS)** and **glypican-1** function as proximal mechanosensors that rapidly trigger NO signaling when mechanically engaged. - Pharmacological perturbation results implicate **TRP-channel-associated Ca2+ entry** in the mechanosignaling pathway: SKF96365 markedly suppressed mechanically evoked NO responses, while amiloride produced a smaller but still significant reduction. - The work highlights glypican-1 engagement and potential **TRP channel** involvement in ESG-mediated mechanotransduction and identifies a technique for probing receptor-to-signal maps relevant to cardiovascular pathologies tied to glycocalyx dysfunction. - The AFM-based force-to-signal approach provides a direct, quantitative, molecule-specific mechanical stimulus coupled to a fluorescent readout, enabling exploration of mechanosensing targets for disease. - Funding sources included NIH grant HL152348 and a University of Massachusetts Amherst Graduate Student Research Grant.
## Clinical Analysis & Structured Key Points
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Online ahead of print. # AFM Force-to-Signal Assay Uncovers Glypican-1 and TRP Channel Roles in Endothelial Mechanotransduction [Matthew A Dragovich](https://pubmed.ncbi.nlm.nih.gov/?term=Dragovich+MA&cauthor_id=42804384)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42804384/#full-view-affiliation-1 "Department of Bioengineering, Lehigh University, Bethlehem, PA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42804384/#full-view-affiliation-2 "Xencor Inc., Los Angeles, CA, USA."), [Xaymara I Rivera Gonzalez](https://pubmed.ncbi.nlm.nih.gov/?term=Rivera+Gonzalez+XI&cauthor_id=42804384)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42804384/#full-view-affiliation-3 "Department of Biomedical Engineering, University of Massachusetts-Amherst, Amherst, MA, USA."), [X Frank Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+XF&cauthor_id=42804384)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42804384/#full-view-affiliation-1 "Department of Bioengineering, Lehigh University, Bethlehem, PA, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42804384/#full-view-affiliation-3 "Department of Biomedical Engineering, University of Massachusetts-Amherst, Amherst, MA, USA.") Affiliations Expand ### Affiliations * 1 Department of Bioengineering, Lehigh University, Bethlehem, PA, USA. * 2 Xencor Inc., Los Angeles, CA, USA. * 3 Department of Biomedical Engineering, University of Massachusetts-Amherst, Amherst, MA, USA. * PMID: **42804384** * DOI: [ 10.1152/ajpheart.90228.2026 ](https://doi.org/10.1152/ajpheart.90228.2026) Item in Clipboard # AFM Force-to-Signal Assay Uncovers Glypican-1 and TRP Channel Roles in Endothelial Mechanotransduction Matthew A Dragovich et al. Am J Physiol Heart Circ Physiol. 2026. Show details Display options Display options Format Abstract PubMed PMID Am J Physiol Heart Circ Physiol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Am+J+Physiol+Heart+Circ+Physiol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Am+J+Physiol+Heart+Circ+Physiol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42804384/) . 2026 Sep 28. doi: 10.1152/ajpheart.90228.2026. Online ahead of print. ### Authors [Matthew A Dragovich](https://pubmed.ncbi.nlm.nih.gov/?term=Dragovich+MA&cauthor_id=42804384)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42804384/#short-view-affiliation-1 "Department of Bioengineering, Lehigh University, Bethlehem, PA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42804384/#short-view-affiliation-2 "Xencor Inc., Los Angeles, CA, USA."), [Xaymara I Rivera Gonzalez](https://pubmed.ncbi.nlm.nih.gov/?term=Rivera+Gonzalez+XI&cauthor_id=42804384)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42804384/#short-view-affiliation-3 "Department of Biomedical Engineering, University of Massachusetts-Amherst, Amherst, MA, USA."), [X Frank Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+XF&cauthor_id=42804384)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42804384/#short-view-affiliation-1 "Department of Bioengineering, Lehigh University, Bethlehem, PA, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42804384/#short-view-affiliation-3 "Department of Biomedical Engineering, University of Massachusetts-Amherst, Amherst, MA, USA.") ### Affiliations * 1 Department of Bioengineering, Lehigh University, Bethlehem, PA, USA. * 2 Xencor Inc., Los Angeles, CA, USA. * 3 Department of Biomedical Engineering, University of Massachusetts-Amherst, Amherst, MA, USA. * PMID: **42804384** * DOI: [ 10.1152/ajpheart.90228.2026 ](https://doi.org/10.1152/ajpheart.90228.2026) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract The endothelial surface glycocalyx (ESG) is a dense, carbohydrate-rich mesh of glycoproteins, proteoglycans, and glycosaminoglycans (GAGs) that coats the surface of endothelial cells (ECs). Mechanical cues, such as shear stress, at the ESG can be rapidly translated into biochemical signals. An impairment in this mechanosignaling pathway is linked to cardiovascular complications, such as diabetes, stroke, sepsis, and atherosclerosis, due to the decrease in the potent vasodilator, nitric oxide (NO). ESG plays a role in this pathway; however, the receptor-level pathways remain obscure. We present an atomic force microscopy (AFM) force-to-signal assay that delivers real-time, pico- to nano-newton, receptor-targeted mechanical inputs to a single live EC while simultaneously recording NO production via fluorescence. We apply controlled pulling forces to ESG components on mouse brain ECs to investigate which ESG elements are relevant to mechanosensing and which transient receptor potential (TRP) ion channels support Ca2+-dependent NO production. Our key findings are the following: (1) heparan sulfate (HS) and glypican-1 act as proximal mechano-sensors that trigger rapid NO signaling. (2) Pharmacological perturbation with SKF96365 markedly suppressed the mechanically evoked NO response, whereas a smaller but significant response persisted in the presence of amiloride. Together, our findings highlight glypican-1 engagement and the potential involvement of TRP-channel-associated Ca2+ entry in the ESG-mediated mechanosignaling pathway. Additionally, by directly coupling a molecule-specific mechanical input to a quantitative fluorescent readout, this technique provides a direct, single-cell map of endothelial mechanotransduction from receptor to downstream signal, enabling exploration of relevant targets for cardiovascular pathologies associated with glycocalyx dysfunction. **Keywords:** Atomic Force Microscopy; Endothelial Surface Glycocalyx; Mechanotransduction; Nitric Oxide Production; TRP Channels. 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