Human brain microvascular endothelial cells resist elongation due to shear stress.
Endothelial cells in straight sections of vessels are known to elongate and align in the direction of flow. This phenotype has been replicated in confluent monolayers of bovine aortic endothelial cells and human umbilical vein endothelial cells (HUVECs) in cell culture under physiological shear stress. Here we report on the morphological response of human brain microvascular endothelial cells (HBMECs) in confluent monolayers in response to shear stress. Using a microfluidic platform we image confluent monolayers of HBMECs and HUVECs under shear stresses up to 16 dyne cm(-2). From live-cell imaging we quantitatively analyze the cell morphology and cell speed as a function of time. We show that HBMECs do not undergo a classical transition from cobblestone to spindle-like morphology in response to shear stress. We further show that under shear stress, actin fibers are randomly oriented in the cells indicating that there is no cytoskeletal remodeling. These results suggest that HBMECs are programmed to resist elongation and alignment under shear stress, a phenotype that may be associated with the unique properties of the blood-brain barrier.
Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Adam
A
Reinitz
Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Jackson
J
DeStefano
Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Mao
M
Ye
Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Andrew D
AD
Wong
Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Institute for Nanobiotechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA. Electronic address: searson@jhu.edu.
Peter C
PC
Searson
D000199:Actins / Q000378:metabolism; D001783:Blood Flow Velocity; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply* / Q000166:cytology; D002460:Cell Line; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D010641:Phenotype; D033081:Shear Strength; D013314:Stress, Mechanical; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D000199:Actins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin
Alignment; Cell morphology; Elongation; Human brain microvascular endothelial cells; Shear stress