title: Endothelial cell alignment as a result of anisotropic strain and flow induced shear stress combinations.
abstract: Endothelial cells (ECs) are continuously exposed in vivo to cyclic strain and shear stress from pulsatile blood flow. When these stimuli are applied in vitro, ECs adopt an appearance resembling their in vivo state, most apparent in their alignment (perpendicular to uniaxial strain and along the flow). Uniaxial strain and flow perpendicular to the strain, used in most in vitro studies, only represent the in vivo conditions in straight parts of vessels. The conditions present over large fractions of the vasculature can be better represented by anisotropic biaxial strains at various orientations to flow. To emulate these biological complexities in vitro, we have developed a medium-throughput device to screen for the effects on cells of variously oriented anisotropic biaxial strains and flow combinations. Upon the application of only strains for 24 h, ECs (HUVECs) aligned perpendicular to the maximum principal strain and the alignment was stronger for a higher maximum:minimum principal strain ratio. A 0.55 Pa shear stress, when applied alone or with strain for 24 h, caused cells to align along the flow. Studying EC response to such combined physiological mechanical stimuli was not possible with existing platforms and to our best knowledge, has not been reported before.
authors.affiliation: Department of Biomechanical Engineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Ravi
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Applied Microfluidics for BioEngineering Research group, MIRA Institute for Biomedical Technology and Technical Medicine, MESA+ Institute for Nanotechnology, University of Twente, Enschede, The Netherlands.
authors.forename: Séverine
authors.initials: S
authors.lastname: Le Gac
authors.affiliation: Department of Biomechanical Engineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.|Radboud university medical center, Radboud Institute for Health Sciences, Orthopaedic Research Lab, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: Verdonschot
authors.affiliation: BIOS, Lab on a chip group, MIRA Institute for Biomedical Technology and Technical Medicine, MESA+ Institute for Nanotechnology, University of Twente, Enschede, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: van den Berg
authors.affiliation: Department of Biomechanical Engineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Koopman
authors.affiliation: Department of Biomechanical Engineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Rouwkema
mesh_terms: D016880:Anisotropy; D002478:Cells, Cultured; D003198:Computer Simulation; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D057446:Hydrodynamics; D011312:Pressure; D033081:Shear Strength; D012984:Software; D013314:Stress, Mechanical
chemical_list: D004129:Dimethylpolysiloxanes; C013830:baysilon