Endothelial Cells Do Not Align with the Mean Wall Shear Stress Vector

Overview

Journal J R Soc Interface

Specialties Biology
Biomedical Engineering
Biophysics

Date 2021 Jan 13

PMID 33435845

Citations 11

Authors

Mehwish Arshad

Mean Ghim

Yumnah Mohamied

Spencer J Sherwin

Peter D Weinberg

Affiliations

Soon will be listed here.

Abstract

The alignment of arterial endothelial cells (ECs) with the mean wall shear stress (WSS) vector is the prototypical example of their responsiveness to flow. However, evidence for this behaviour rests on experiments where many WSS metrics had the same orientation or where they were incompletely characterized. In the present study, we tested the phenomenon more rigorously. Aortic ECs were cultured in cylindrical wells on the platform of an orbital shaker. In this system, orientation would differ depending on the WSS metric to which the cells aligned. Variation in flow features and hence in possible orientations was further enhanced by altering the viscosity of the medium. Orientation of endothelial nuclei was compared with WSS characteristics obtained by computational fluid dynamics. At low mean WSS magnitudes, ECs aligned with the modal WSS vector, while at high mean WSS magnitudes they aligned so as to minimize the shear acting across their long axis (transverse WSS). Their failure to align with the mean WSS vector implies that other aspects of endothelial behaviour attributed to this metric require re-examination. The evolution of a mechanism for minimizing transverse WSS is consistent with it having detrimental effects on the cells and with its putative role in atherogenesis.

Citing Articles

Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions.

Tanaka K, Chen M, Prendergast A, Zhuang Z, Nasiri A, Joshi D EMBO J. 2024; 43(15):3175-3191.

PMID: 38886581 PMC: 11294477. DOI: 10.1038/s44318-024-00142-0.

Full-scale numerical simulation of hemodynamics based on left ventricular assist device.

Gao X, Xu Z, Chen C, Hao P, He F, Zhang X Front Physiol. 2023; 14:1192610.

PMID: 37304828 PMC: 10248007. DOI: 10.3389/fphys.2023.1192610.

Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-β-catenin-dependent pathway.

Rickman M, Ghim M, Pang K, von Huelsen Rocha A, Drudi E, Sureda-Vives M J Cell Sci. 2023; 136(6).

PMID: 36846872 PMC: 10112981. DOI: 10.1242/jcs.260449.

Modification of the swirling well cell culture model to alter shear stress metrics.

Arshad M, Cheng S, van Reeuwijk M, Sherwin S, Weinberg P Biotechnol Bioeng. 2023; 120(5):1254-1268.

PMID: 36633017 PMC: 10952219. DOI: 10.1002/bit.28331.

Characterizing nuclear morphology and expression of eNOS in vascular endothelial cells subjected to a continuous range of wall shear stress magnitudes and directionality.

Sahni J, Arshad M, Schake M, Brooks J, Yang R, Weinberg P J Mech Behav Biomed Mater. 2022; 137:105545.

PMID: 36368188 PMC: 10371053. DOI: 10.1016/j.jmbbm.2022.105545.

References

Butcher J, Penrod A, Garcia A, Nerem R . Unique morphology and focal adhesion development of valvular endothelial cells in static and fluid flow environments. Arterioscler Thromb Vasc Biol. 2004; 24(8):1429-34. DOI: 10.1161/01.ATV.0000130462.50769.5a. View

Liepsch D, Levesque M, Nerem R, Moravec S . Correlation of laser-Doppler-velocity measurements and endothelial cell shape in a stenosed dog aorta. Adv Exp Med Biol. 1988; 242:43-50. DOI: 10.1007/978-1-4684-8935-4_6. View

He X, Ku D . Pulsatile flow in the human left coronary artery bifurcation: average conditions. J Biomech Eng. 1996; 118(1):74-82. DOI: 10.1115/1.2795948. View

Dekker R, van Thienen J, Rohlena J, de Jager S, Elderkamp Y, Seppen J . Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes. Am J Pathol. 2005; 167(2):609-18. PMC: 1603569. DOI: 10.1016/S0002-9440(10)63002-7. View

Hazel A, Pedley T . Vascular endothelial cells minimize the total force on their nuclei. Biophys J. 2000; 78(1):47-54. PMC: 1300616. DOI: 10.1016/S0006-3495(00)76571-4. View

Givens C, Tzima E . Endothelial Mechanosignaling: Does One Sensor Fit All?. Antioxid Redox Signal. 2016; 25(7):373-88. PMC: 5011625. DOI: 10.1089/ars.2015.6493. View

Ku D, Giddens D, Zarins C, Glagov S . Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis. 1985; 5(3):293-302. DOI: 10.1161/01.atv.5.3.293. View

Vamsi Krishna C, Suja V, Watton P, Arakeri J, Gundiah N . Shear stress rosettes capture the complex flow physics in diseased arteries. J Biomech. 2020; 104:109721. DOI: 10.1016/j.jbiomech.2020.109721. View

Barbee K, Mundel T, Lal R, Davies P . Subcellular distribution of shear stress at the surface of flow-aligned and nonaligned endothelial monolayers. Am J Physiol. 1995; 268(4 Pt 2):H1765-72. DOI: 10.1152/ajpheart.1995.268.4.H1765. View

10.

Yamaguchi T, Yamamoto Y, Liu H . Computational mechanical model studies on the spontaneous emergent morphogenesis of the cultured endothelial cells. J Biomech. 1999; 33(1):115-26. DOI: 10.1016/s0021-9290(99)00159-1. View

11.

Hahn C, Wang C, Orr A, Coon B, Schwartz M . JNK2 promotes endothelial cell alignment under flow. PLoS One. 2011; 6(8):e24338. PMC: 3164210. DOI: 10.1371/journal.pone.0024338. View

12.

Flaherty J, Pierce J, Ferrans V, Patel D, Tucker W, FRY D . Endothelial nuclear patterns in the canine arterial tree with particular reference to hemodynamic events. Circ Res. 1972; 30(1):23-33. DOI: 10.1161/01.res.30.1.23. View

13.

Chakraborty A, Chakraborty S, Jala V, Haribabu B, Sharp M, Eric Berson R . Effects of biaxial oscillatory shear stress on endothelial cell proliferation and morphology. Biotechnol Bioeng. 2011; 109(3):695-707. DOI: 10.1002/bit.24352. View

14.

Morbiducci U, Gallo D, Cristofanelli S, Ponzini R, Deriu M, Rizzo G . A rational approach to defining principal axes of multidirectional wall shear stress in realistic vascular geometries, with application to the study of the influence of helical flow on wall shear stress directionality in aorta. J Biomech. 2015; 48(6):899-906. DOI: 10.1016/j.jbiomech.2015.02.027. View

15.

Dardik A, Chen L, Frattini J, Asada H, Aziz F, Kudo F . Differential effects of orbital and laminar shear stress on endothelial cells. J Vasc Surg. 2005; 41(5):869-80. DOI: 10.1016/j.jvs.2005.01.020. View

16.

Caro C, Fitz-Gerald J, Schroter R . Atheroma and arterial wall shear. Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis. Proc R Soc Lond B Biol Sci. 1971; 177(1046):109-59. DOI: 10.1098/rspb.1971.0019. View

17.

Chien S, Li S, Shyy Y . Effects of mechanical forces on signal transduction and gene expression in endothelial cells. Hypertension. 1998; 31(1 Pt 2):162-9. DOI: 10.1161/01.hyp.31.1.162. View

18.

Warboys C, Ghim M, Weinberg P . Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method. Atherosclerosis. 2019; 285:170-177. PMC: 6570700. DOI: 10.1016/j.atherosclerosis.2019.04.210. View

19.

Boon R, Leyen T, Fontijn R, Fledderus J, Baggen J, Volger O . KLF2-induced actin shear fibers control both alignment to flow and JNK signaling in vascular endothelium. Blood. 2009; 115(12):2533-42. DOI: 10.1182/blood-2009-06-228726. View

20.

Mohamied Y, Rowland E, Bailey E, Sherwin S, Schwartz M, Weinberg P . Change of direction in the biomechanics of atherosclerosis. Ann Biomed Eng. 2014; 43(1):16-25. PMC: 4286626. DOI: 10.1007/s10439-014-1095-4. View