Speaker: Lowell Taylor Edgar. Advisor: Jeffrey A. Weiss, Ph.D.

Abstract:

Mechanical properties of the extracellular matrix (ECM) such as fiber orientation, density, and boundary conditions regulate neovessel growth and branching during in vitro angiogenesis. Neovessels apply traction and remodel the matrix, forming a positive feedback loop in which growth is regulated by a dynamic ECM. The mechanisms behind this regulation are poorly understood. This lack of understanding arises predominately from the difficultly in establishing cause-effect relationships across length scales in the laboratory (i.e. conditions prescribed globally affect interactions at the microscale). For this reason, we have turned to computational modeling to supplement our experimental investigations into the role of microscale mechanics during angiogenesis. Computational modeling allows us to isolate components of angiogenesis that we can’t isolate and study within the lab. We propose a computational framework in which the feedback loop between neovessels and the ECM will be represented using two coupled components: a growth model that generates microvascular geometry based on properties of the ECM, and software for solid mechanics which can be used to represent cell-generated forces and calculate the deformation of the ECM. The coupling between these two components will occur as kinematics from the solid mechanics software is fed back to regulate the growth model. This computational model will be calibrated and validated using experimental data. Using this framework, we aim to explain observed experimental results, perform parametric studies, and identify the biomechanical mechanisms guiding angiogenesis. To our knowledge, no other researchers have investigated the relationship between morphogenic processes and matrix deformation in such a way. This modeling protocol can be extended to a wide range of potential applications, including simulations of cellular motility, dynamic growth, and tissue morphogenesis.