Microvascular endothelial cells migrate upstream and align against the shear stress field created by impinging flow.
At present, little is known about how endothelial cells respond to spatial variations in fluid shear stress such as those that occur locally during embryonic development, at heart valve leaflets, and at sites of aneurysm formation. We built an impinging flow device that exposes endothelial cells to gradients of shear stress. Using this device, we investigated the response of microvascular endothelial cells to shear-stress gradients that ranged from 0 to a peak shear stress of 9-210 dyn/cm(2). We observe that at high confluency, these cells migrate against the direction of fluid flow and concentrate in the region of maximum wall shear stress, whereas low-density microvascular endothelial cells that lack cell-cell contacts migrate in the flow direction. In addition, the cells align parallel to the flow at low wall shear stresses but orient perpendicularly to the flow direction above a critical threshold in local wall shear stress. Our observations suggest that endothelial cells are exquisitely sensitive to both magnitude and spatial gradients in wall shear stress. The impinging flow device provides a, to our knowledge, novel means to study endothelial cell migration and polarization in response to gradients in physical forces such as wall shear stress.
Chemical Engineering, Stanford University, Stanford, California.
Maggie A
MA
Ostrowski
Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Stanford Cardiovascular Institute, Stanford University, Stanford, Califiornia; Division of Cardiovascular Medicine, Stanford University, Stanford, California.
Ngan F
NF
Huang
Chemical Engineering, Stanford University, Stanford, California.
Travis W
TW
Walker
Department of Chemical Engineering, KU Leuven, Belgium.
Tom
T
Verwijlen
Chemical Engineering, Stanford University, Stanford, California.
Charlotte
C
Poplawski
Division of Cardiovascular Medicine, Stanford University, Stanford, California.
Amanda S
AS
Khoo
Stanford Cardiovascular Institute, Stanford University, Stanford, Califiornia; Division of Cardiovascular Medicine, Stanford University, Stanford, California.
John P
JP
Cooke
Chemical Engineering, Stanford University, Stanford, California. Electronic address: ggf@stanford.edu.
Gerald G
GG
Fuller
Chemical Engineering, Stanford University, Stanford, California; Stanford Cardiovascular Institute, Stanford University, Stanford, Califiornia. Electronic address: alex.dunn@stanford.edu.
Alexander R
AR
Dunn
D002465:Cell Movement; D020342:Finite Element Analysis; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D057446:Hydrodynamics; D008422:Materials Testing / Q000295:instrumentation*; D055806:Microvessels / Q000166:cytology*; D057054:Molecular Imaging; D013314:Stress, Mechanical