biostudies-literatureBosworth AMNIBIB NIH HHS31-42https://www.ebi.ac.uk/biostudies/studies/S-EPMC8761195biostudies-literatureUnknown15(1)<h4>Introduction</h4>Vascular 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 <i>in vitro</i> model of the human BBB.<h4>Methods</h4>Induced 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 electCellular and molecular bioengineeringInfluence of Substrate Stiffness on Barrier Function in an iPSC-Derived <i>In Vitro</i> Blood-Brain Barrier Model.PMC8761195K01 EB030039Bosworth AMRichter IKim HLee LO'Grady BJLippmann ESO'Grady KPfalseInfluence of Substrate Stiffness on Barrier Function in an iPSC-Derived <i>In Vitro</i> Blood-Brain Barrier Model.<h4>Introduction</h4>Vascular 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 <i>in vitro</i> model of the human BBB.<h4>Methods</h4>Induced 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 elect2022-01-01T00:00:00Z2022 Feb2025-06-01T02:24:45.321Z2025-06-01T02:24:45.321ZS-EPMC87611953509618510.1007/s12195-021-00706-8