Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells
Abstract Brain endothelial cells experience mechanical forces in the form of blood flow-mediated shear stress and underlying matrix stiffness, but intersectional contributions of these factors towards blood–brain barrier (BBB) impairment and neurovascular dysfunction have not been extensively studie...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Fluids and Barriers of the CNS |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12987-025-00683-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849761467833778176 |
|---|---|
| author | Alexis K. Yates Heather Murray Andrew Kjar Daniel Chavarria Haley Masters Hyosung Kim Alexander P. Ligocki Angela L. Jefferson Ethan S. Lippmann |
| author_facet | Alexis K. Yates Heather Murray Andrew Kjar Daniel Chavarria Haley Masters Hyosung Kim Alexander P. Ligocki Angela L. Jefferson Ethan S. Lippmann |
| author_sort | Alexis K. Yates |
| collection | DOAJ |
| description | Abstract Brain endothelial cells experience mechanical forces in the form of blood flow-mediated shear stress and underlying matrix stiffness, but intersectional contributions of these factors towards blood–brain barrier (BBB) impairment and neurovascular dysfunction have not been extensively studied. Here, we developed in vitro models to examine the sensitivity of primary human brain microvascular endothelial cells (BMECs) to substrate stiffness, with or without exposure to fluid shear stress. Using a combination of molecular profiling techniques, we show that BMECs exhibit an inflammatory signature at both the mRNA and protein level when cultured on gelatin substrates of intermediate stiffness (~ 30 kPa) versus soft substrates (~ 6 kPa). Exposure to modest fluid shear stress (1.7 dyne/cm2) partially attenuated this signature, including reductions in levels of soluble chemoattractants and surface ICAM-1. Overall, our results indicate that increased substrate stiffness promotes an inflammatory phenotype in BMECs that is dampened in the presence of fluid shear stress. |
| format | Article |
| id | doaj-art-6743328d61c44f6e97c8d1faa9f11fa2 |
| institution | DOAJ |
| issn | 2045-8118 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj-art-6743328d61c44f6e97c8d1faa9f11fa22025-08-20T03:06:01ZengBMCFluids and Barriers of the CNS2045-81182025-07-0122112110.1186/s12987-025-00683-4Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cellsAlexis K. Yates0Heather Murray1Andrew Kjar2Daniel Chavarria3Haley Masters4Hyosung Kim5Alexander P. Ligocki6Angela L. Jefferson7Ethan S. Lippmann8Interdisciplinary Materials Science Program, Vanderbilt UniversityChemical and Biomolecular Engineering Department, Vanderbilt UniversityBiomedical Engineering Department, Vanderbilt UniversityChemical and Biomolecular Engineering Department, Vanderbilt UniversityChemical and Biomolecular Engineering Department, Vanderbilt UniversityChemical and Biomolecular Engineering Department, Vanderbilt UniversityChemical and Biomolecular Engineering Department, Vanderbilt UniversityVanderbilt Memory and Alzheimer’s Center, Vanderbilt University Medical CenterInterdisciplinary Materials Science Program, Vanderbilt UniversityAbstract Brain endothelial cells experience mechanical forces in the form of blood flow-mediated shear stress and underlying matrix stiffness, but intersectional contributions of these factors towards blood–brain barrier (BBB) impairment and neurovascular dysfunction have not been extensively studied. Here, we developed in vitro models to examine the sensitivity of primary human brain microvascular endothelial cells (BMECs) to substrate stiffness, with or without exposure to fluid shear stress. Using a combination of molecular profiling techniques, we show that BMECs exhibit an inflammatory signature at both the mRNA and protein level when cultured on gelatin substrates of intermediate stiffness (~ 30 kPa) versus soft substrates (~ 6 kPa). Exposure to modest fluid shear stress (1.7 dyne/cm2) partially attenuated this signature, including reductions in levels of soluble chemoattractants and surface ICAM-1. Overall, our results indicate that increased substrate stiffness promotes an inflammatory phenotype in BMECs that is dampened in the presence of fluid shear stress.https://doi.org/10.1186/s12987-025-00683-4Brain microvascular endothelial cellVascular stiffeningFluid shear stressIn vitro modelsInflammation |
| spellingShingle | Alexis K. Yates Heather Murray Andrew Kjar Daniel Chavarria Haley Masters Hyosung Kim Alexander P. Ligocki Angela L. Jefferson Ethan S. Lippmann Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells Fluids and Barriers of the CNS Brain microvascular endothelial cell Vascular stiffening Fluid shear stress In vitro models Inflammation |
| title | Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells |
| title_full | Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells |
| title_fullStr | Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells |
| title_full_unstemmed | Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells |
| title_short | Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells |
| title_sort | substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells |
| topic | Brain microvascular endothelial cell Vascular stiffening Fluid shear stress In vitro models Inflammation |
| url | https://doi.org/10.1186/s12987-025-00683-4 |
| work_keys_str_mv | AT alexiskyates substratestiffnessandshearstresscollectivelyregulatetheinflammatoryphenotypeinculturedhumanbrainmicrovascularendothelialcells AT heathermurray substratestiffnessandshearstresscollectivelyregulatetheinflammatoryphenotypeinculturedhumanbrainmicrovascularendothelialcells AT andrewkjar substratestiffnessandshearstresscollectivelyregulatetheinflammatoryphenotypeinculturedhumanbrainmicrovascularendothelialcells AT danielchavarria substratestiffnessandshearstresscollectivelyregulatetheinflammatoryphenotypeinculturedhumanbrainmicrovascularendothelialcells AT haleymasters substratestiffnessandshearstresscollectivelyregulatetheinflammatoryphenotypeinculturedhumanbrainmicrovascularendothelialcells AT hyosungkim substratestiffnessandshearstresscollectivelyregulatetheinflammatoryphenotypeinculturedhumanbrainmicrovascularendothelialcells AT alexanderpligocki substratestiffnessandshearstresscollectivelyregulatetheinflammatoryphenotypeinculturedhumanbrainmicrovascularendothelialcells AT angelaljefferson substratestiffnessandshearstresscollectivelyregulatetheinflammatoryphenotypeinculturedhumanbrainmicrovascularendothelialcells AT ethanslippmann substratestiffnessandshearstresscollectivelyregulatetheinflammatoryphenotypeinculturedhumanbrainmicrovascularendothelialcells |