title: Flow dynamics control the location of sprouting and direct elongation during developmental angiogenesis.
abstract: Angiogenesis is tightly controlled by a number of signalling pathways. Although our understanding of the molecular mechanisms involved in angiogenesis has rapidly increased, the role that biomechanical signals play in this process is understudied. We recently developed a technique to simultaneously analyse flow dynamics and vascular remodelling by time-lapse microscopy in the capillary plexus of avian embryos and used this to study the hemodynamic environment present during angiogenic sprouting. We found that sprouts always form from a vessel at lower pressure towards a vessel at higher pressure, and that sprouts form at the location of a shear stress minimum, but avoid locations where two blood streams merge even if this point is at a lower level of shear stress than the sprouting location. Using these parameters, we were able to successfully predict sprout location in quail embryos. We also found that the pressure difference between two vessels is permissive to elongation, and that sprouts will either change direction or regress if the pressure difference becomes negative. Furthermore, the sprout elongation rate is proportional to the pressure difference between the two vessels. Our results show that flow dynamics are predictive of the location of sprout formation in perfused vascular networks and that pressure differences across the interstitium can guide sprout elongation.
authors.affiliation: Lady Davis Institute for Medical Research, McGill University, 3755 Chemin de la Côte-Ste-Catherine, Montréal, Quebec H3T 1E2, Canada Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, Quebec H3A 0C5, Canada.
authors.forename: Siavash
authors.initials: S
authors.lastname: Ghaffari
authors.affiliation: Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, Quebec H3A 0C5, Canada.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Leask
authors.affiliation: Lady Davis Institute for Medical Research, McGill University, 3755 Chemin de la Côte-Ste-Catherine, Montréal, Quebec H3T 1E2, Canada Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, Quebec H3A 0C5, Canada Department of Cardiovascular Science, KU Leuven, UZ Herestraat 49, Box 911, Leuven 3000, Belgium liz.jones@med.kuleuven.be.
authors.forename: Elizabeth A V
authors.initials: EA
authors.lastname: Jones
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D042783:Endothelial Cells / Q000166:cytology; D006439:Hemodynamics; D057446:Hydrodynamics; D007091:Image Processing, Computer-Assisted; D008856:Microscopy, Fluorescence; D009024:Morphogenesis; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011312:Pressure; D011784:Quail / Q000196:embryology*; D033081:Shear Strength; D013314:Stress, Mechanical; D059008:Time-Lapse Imaging
keywords: Angiogenesis; Computational fluid dynamics; Hemodynamics; Micro-particle image velocimetry; Time-lapse microscopy