Mechanotransmission in endothelial cells subjected to oscillatory and multi-directional shear flow.

Journal Article

Local haemodynamics are linked to the non-uniform distribution of atherosclerosic lesions in arteries. Low and oscillatory (reversing in the axial flow direction) wall shear stress (WSS) induce inflammatory responses in endothelial cells (ECs) mediating disease localization. The objective of this study is to investigate computationally how the flow direction (reflected in WSS variation on the EC surface over time) influences the forces experienced by structural components of ECs that are believed to play important roles in mechanotransduction. A three-dimensional, multi-scale, multi-component, viscoelastic model of focally adhered ECs is developed, in which oscillatory WSS (reversing or non-reversing) parallel to the principal flow direction, or multi-directional oscillatory WSS with reversing axial and transverse components are applied over the EC surface. The computational model includes the glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs), stress fibres and adherens junctions (ADJs). We show the distinct effects of atherogenic flow profiles (reversing unidirectional flow and reversing multi-directional flow) on subcellular structures relative to non-atherogenic flow (non-reversing flow). Reversing flow lowers stresses and strains due to viscoelastic effects, and multi-directional flow alters stress on the ADJs perpendicular to the axial flow direction. The simulations predict forces on integrins, ADJ filaments and other substructures in the range that activate mechanotransduction.

Full Text

Duke Authors

Cited Authors

  • Dabagh, M; Jalali, P; Butler, PJ; Randles, A; Tarbell, JM

Published Date

  • May 2017

Published In

Volume / Issue

  • 14 / 130

PubMed ID

  • 28515328

Electronic International Standard Serial Number (EISSN)

  • 1742-5662

International Standard Serial Number (ISSN)

  • 1742-5689

Digital Object Identifier (DOI)

  • 10.1098/rsif.2017.0185

Language

  • eng