ArticleACS nano2022
Substrate Stiffness-Driven Membrane Tension Modulates Vesicular Trafficking
Article in ACS nano, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Mechanically Regulated Secretion: How Physical Forces Instruct the Secretory Pathway and Remodel the Secretome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Phospholipase D2 acts upstream of PI4P 5-kinases in the response of neurons to extracellular viscosity.iScience · 2026Article
- New approach methodologies (NAMs) for preclinical and translational evaluation of mRNA-lipid nanoparticle (LNP) therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- Matrix Stiffness Enhances Odontogenic Differentiation of DPSCs through Membrane Curvature Protein Baiap2-Modulated Exosome Release.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Loading is not delivering: Intracellular drug retention and migration capacity govern macrophage-based drug delivery.Science advances · 2026Article
- Membrane remodeling by the collective action of caveolin-1.Nature communications · 2026Article
- Acidosis Regulates Microtubule Dynamics via the β1 Integrin/RhoA/CRMP-2 Axis.Journal of the American Chemical Society · 2026Article
- Cracking the shield: oncolytic viruses versus the tumor-immune fortress.Cancer cell international · 2026Review
- Orai1 is required for CabioRxiv : the preprint server for biology · 2026Article
- Viscoelastic hydrogel primed CAR-macrophage for pulmonary fibrosis treatment.Nature communications · 2026Article
- Matrix stiffness may drive multi-cellular crosstalk via YAP signaling in biliary atresia liver fibrosis: a mechanistic review.Frontiers in cell and developmental biology · 2026Review
- Mechanical Cues Regulate Cargo Sorting and Export at the Golgi.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Substrate Stiffness Modulates Fibroblast Extracellular Vesicle Secretion Via Mechanotransduction Pathways.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Membrane Remodeling by the Collective Action of Caveolin-1.bioRxiv : the preprint server for biology · 2025Article
- Stiffness-activated hepatic stellate cells boost HCC migration via TGM2/ITGB1-mediated matrix remodeling and mitochondrial transfer.JHEP reports : innovation in hepatology · 2025Article
- Optimizing standardized lab-grown skin substitutes evidences a proliferation-differentiation switch based on ascorbic acid.iScience · 2025Article
- Inhibition of the Caveolin-1 pathway promotes apoptosis and overcomes pan-tyrosine kinase inhibitor resistance in hepatocellular carcinoma.Cell death & disease · 2025Article
- External strain on the plasma membrane is relayed to the endoplasmic reticulum by membrane contact sites and alters cellular energetics.Science advances · 2025Article
- Scaffold Proteins in Fibrotic Diseases of Visceral Organs.Biomolecules · 2025Review
- Tension-induced organelle stress: an emerging target in fibrosis.Trends in pharmacological sciences · 2025Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Liver fibrosis, a condition characterized by extensive deposition and cross-linking of extracellular matrix (ECM) proteins, is idiosyncratic in cases of chronic liver injury. The dysregulation of ECM remodeling by hepatic stellate cells (HSCs), the main mediators of fibrosis, results in an elevated ECM stiffness that drives the development of chronic liver disease such as cirrhosis and hepatocellular carcinoma. Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is a key element in the regulation of ECM remodeling, which modulates the degradation and turnover of ECM components. We have previously reported that a rigid, fibrotic-like substrate can impact TIMP-1 expression at the protein level in HSCs without altering its mRNA expression. While HSCs are known to be highly susceptible to mechanical stimuli, the mechanisms through which mechanical cues regulate TIMP-1 at the post-translational level remain unclear. Here, we show a mechanism of regulation of plasma membrane tension by matrix stiffness. We found that this effect is orchestrated by the β1 integrin/RhoA axis and results in elevated exocytosis and secretion of TIMP-1 in a caveolin-1- and dynamin-2-dependent manner. We then show that TIMP-1 and caveolin-1 expression increases in cirrhosis and hepatocellular carcinoma. These conditions are associated with fibrosis, and this effect can be recapitulated in 3D fibrosis models consisting of hepatic stellate cells encapsulated in a self-assembling polypeptide hydrogel. This work positions stiffness-dependent membrane tension as a key regulator of enzyme secretion and function and a potential target for therapeutic strategies that aim at modulating ECM remodeling in chronic liver disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.