Interaction of Angiogenic Microvessels with the Extracellular Matrix

Jeffrey A. Weiss, PhD
Professor of Bioengineering
Adjunct Professor of Orthopaedics and School of Computing
Faculty Member, Scientific Computing and Imaging Institute
The University of Utah

The motility and proliferation of angiogenic neovessels are modulated by the material properties of the extracellular matrix (ECM).  Neovessels also modify the material properties of the ECM as they migrate through and interact with the ECM.  This creates a dynamic feedback loop in which angiogenesis is coupled with deformation and remodeling of the ECM.  In this talk, he will discuss their experimental and computational research to investigate this phenomenon.  The experimental aspects of the research are based on a 3D in vitro organ culture model of sprouting angiogenesis.  The computational approach is based on coupling a validated model of angiogenic growth with the FEBio finite element software framework developed in their laboratory (www.febio.org).  In these studies they demonstrate that angiogenic neovessels extensively deform and remodel the ECM through a combination of cellular traction forces, proteolytic activity and generation of new cell-matrix adhesions.  Sensitivity analysis using their computational model demonstrated that cell-generated traction during growth is the most important parameter controlling the deformation of the matrix and therefore angiogenic growth, remodeling and morphometry of the resulting microvascular bed.  Live, large-scale mulitphoton imaging elucidated several neovessel behaviors during angiogenesis that are poorly understood such as episodic growth/regression, neovessel co-location, and anastomosis.  The combined approach has allowed them to demonstrate that angiogenic growth and the resulting topology of a vascular network can be manipulated directly by altering the mechanical interactions between cells and the ECM.