ArticleIntegrative biology : quantitative biosciences from nano to macro2018
Substrate stiffness heterogeneities disrupt endothelial barrier integrity in a micropillar model of heterogeneous vascular stiffening.
Article in Integrative biology : quantitative biosciences from nano to macro, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Vascular endothelial integration of multiple biophysical stimuli.Frontiers in cardiovascular medicine · 2026Article
- Diabetic hyperglycemia-induced glycation regulates tumor vasculature integrity via NF-κB-mediated GM-CSF secretion by tumor cells.Cell biomaterials · 2025Article
- A mechanical modeling framework to study endothelial permeability.Biophysical journal · 2024Article
- Impact of adhesive area on cellular traction force and spread area.Journal of biomedical materials research. Part A · 2023Article
- Influence of PHA Substrate Surface Characteristics on the Functional State of Endothelial Cells.Journal of functional biomaterials · 2023Article
- Engineering of the microenvironment to accelerate vascular regeneration.Trends in molecular medicine · 2023Review
- The cellular mechanobiology of aging: from biology to mechanics.Annals of the New York Academy of Sciences · 2021Review
- Inspired by the human placenta: a novel 3D bioprinted membrane system to create barrier models.Scientific reports · 2020Article
- A discrete interface in matrix stiffness creates an oscillatory pattern of endothelial monolayer disruption.Journal of cell science · 2020Article
- Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology.Advanced healthcare materials · 2020Review
- Coupling Microfluidic Platforms, Microfabrication, and Tissue Engineered Scaffolds to Investigate Tumor Cells Mechanobiology.Micromachines · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Intimal stiffening has been linked with increased vascular permeability and leukocyte transmigration, hallmarks of atherosclerosis. However, recent evidence indicates age-related intimal stiffening is not uniform but rather characterized by increased point-to-point heterogeneity in subendothelial matrix stiffness, the impact of which is much less understood. To investigate the impact of spatially heterogeneous matrix rigidity on endothelial monolayer integrity, we develop a micropillar model to introduce closely-spaced, step-changes in substrate rigidity and compare endothelial monolayer phenotype to rigidity-matched, uniformly stiff and compliant substrates. We found equivalent disruption of adherens junctions within monolayers on step-rigidity and uniformly stiff substrates relative to uniformly compliant substrates. Similarly, monolayers cultured on step-rigidity substrates exhibited equivalent percentages of leukocyte transmigration to monolayers on rigidity-matched, uniformly stiff substrates. Adherens junction tension and focal adhesion density, but not size, increased within monolayers on step-rigidity and uniformly stiff substrates compared to more compliant substrates suggesting that elevated tension is disrupting adherens junction integrity. Leukocyte transmigration frequency and time, focal adhesion size, and focal adhesion density did not differ between stiff and compliant sub-regions of step-rigidity substrates. Overall, our results suggest that endothelial monolayers exposed to mechanically heterogeneous substrates adopt the phenotype associated with the stiffer matrix, indicating that spatial heterogeneities in intimal stiffness observed with age could disrupt endothelial barrier integrity and contribute to atherogenesis.
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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.