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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, I will discuss our experimental and computational research to investigate the 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 our laboratory (www.febio.org). In these studies we 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 our 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 us 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.
Dr. Jeff Weiss, Department of Bioengineering, University of Utah
Presented September 16, 2016
About the Presenter
About the Presenter
Professor Jeff Weiss received his bachelor’s and master’s degrees in Bioengineering at the University of California, San Diego, his doctorate in Bioengineering at the University of Utah in 1994, and completed postdoctoral training with the Applied Mechanics Group at Lawrence Livermore National Laboratory (1995-96). He holds the titles of Professor of Bioengineering, Adjunct Professor in the School of Computing, Adjunct Professor of Orthopedics, and Faculty Member in the Scientific Computing and Imaging Institute at the University of Utah.
Weiss’ research efforts have focused on the areas of experimental and computational biomechanics, primarily applied to the musculoskeletal and cardiovascular soft tissues. He developed and validated techniques for subject-specific computational modeling of joint mechanics, and applied these techniques to the mechanics of knee ligaments and patient-specific modeling of mechanics in the hip. Fundamental studies of ligament and tendon mechanics have included constitutive modeling, elucidation of ligament in situ strains, characterization of multiaxial viscoelastic material behavior, characterization of structure-function relationships, and determining the structural role of non-collagenous components, including decorin proteoglycans and elastin. Professor Weiss also developed finite-element based techniques to incorporate medical image data directly into biomechanics analyses for strain measurement. His current research interests include the mechanics of angiogenesis, the development of patient-specific analysis methods for joint and tissue mechanics, structure-function relationships in ligaments and tendons, and the development of distribution of software for computational biomechanics. Professor Weiss’s lab develops, distributes and supports FEBio, an open-source finite element software suite for computational biomechanics (www.febio.org).
Professor Weiss has received a number of highly coveted honors, including a Whitaker Foundation Research Grant (1995), a NSF CAREER Award (2002), the ASME YC Fung Young Investigator Award (2002), Election to Fellow of the AIMBE (2006), the ASME Van C. Model Medal (2013) and several Best Paper awards.
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