ArticleCellular and molecular bioengineering2022
Influence of Substrate Stiffness on Barrier Function in an iPSC-Derived
Article in Cellular and molecular bioengineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- A Physiological Microfluidic Blood-Brain-Barrier Model for In Vitro Study of Nanoparticle Trafficking and Accumulation.Advanced healthcare materials · 2026Article
- ECM stiffness governs endothelial barrier integrity through YAP-mediated stabilization of ZO-1.Bioactive materials · 2026Article
- Substrate stiffness and cellular microenvironment regulate cell and junction mechanics in iPSC-derived brain microvascular endothelial cells.bioRxiv : the preprint server for biology · 2026Article
- Making tracks: microglia and the extracellular matrix.Molecular neurodegeneration · 2025Review
- A physiological microfluidic blood-brain-barrier model for in vitro study of nanoparticle trafficking and accumulation.bioRxiv : the preprint server for biology · 2025Article
- Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells.Fluids and barriers of the CNS · 2025Article
- Exploring dysfunctional barrier phenotypes associated with glaucoma using a human pluripotent stem cell-based model of the neurovascular unit.Fluids and barriers of the CNS · 2024Article
- Oligomeric Amyloid-β and Tau Alter Cell Adhesion Properties and Induce Inflammatory Responses in Cerebral Endothelial Cells Through the RhoA/ROCK Pathway.Molecular neurobiology · 2024Article
- Modular tissue-in-a-CUBE platform to model blood-brain barrier (BBB) and brain interaction.Communications biology · 2024Article
- A Rapid-Patterning 3D Vessel-on-Chip for Imaging and Quantitatively Analyzing Cell-Cell Junction Phenotypes.Bioengineering (Basel, Switzerland) · 2023Article
- Control of blood capillary networks and holes in blood-brain barrier models by regulating elastic modulus of scaffolds.Materials today. Bio · 2023Article
- Organ-Specific Endothelial Cell Differentiation and Impact of Microenvironmental Cues on Endothelial Heterogeneity.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
introductionVascular endothelial cells respond to a variety of biophysical cues such as shear stress and substrate stiffness. In peripheral vasculature, extracellular matrix (ECM) stiffening alters barrier function, leading to increased vascular permeability in atherosclerosis and pulmonary edema. The effect of ECM stiffness on blood-brain barrier (BBB) endothelial cells, however, has not been explored. To investigate this topic, we incorporated hydrogel substrates into an
methodsInduced pluripotent stem cells were differentiated to brain microvascular endothelial-like (BMEC-like) cells and cultured on hydrogel substrates of varying stiffness. Cellular changes were measured by imaging, functional assays such as transendothelial electrical resistance (TEER) and p-glycoprotein efflux activity, and bulk transcriptome readouts.
resultsThe magnitude and longevity of TEER in iPSC-derived BMEC-like cells is enhanced on compliant substrates. Quantitative imaging shows that BMEC-like cells form fewer intracellular actin stress fibers on substrates of intermediate stiffness (20 kPa relative to 1 and 150 kPa). Chemical induction of actin polymerization leads to a rapid decline in TEER, agreeing with imaging readouts. P-glycoprotein activity is unaffected by substrate stiffness. Modest differences in RNA expression corresponding to specific signaling pathways were observed as a function of substrate stiffness.
conclusionsiPSC-derived BMEC-like cells exhibit differences in passive but not active barrier function in response to substrate stiffness. These findings may provide insight into BBB dysfunction during neurodegeneration, as well as aid in the optimization of more complex three-dimensional neurovascular models utilizing compliant hydrogels. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00706-8.
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