Coordinated endothelial cell networking, a component of angiogenesis, is required to form and refine the exquisite fractal network that emerges in the developing and mature lung to facilitate efficient gas exchange from birth onwards. Real-time imaging of endothelial cells cultured within a specialized extracellular matrix (ECM) microenvironment, designated the basement membrane, and formed the basis of this project. The angiogenic networking behavior of lung mesenchymal cells, designated RFL-6 or MFLM-4 cells, which have ability to transform into networking endothelial cells in response to basement membrane proteins was evaluated in contrasting conditions: with or without Prx-1, a gene that enhances networking. When Prx-1 is absent, cells formed clustered on basement membrane material. On the other hand, when Prx-1 was present, cells formed branched networks on this matrix. These formations are also influenced by the flow paths or topological geometries found within the underlying ECM. Thus, the roles played by Prx-1 (code) and the ECM (environment) are highly influential in creating these network morphologies by endothelial cells (components).
UPenn Dept of ARCH745, Nonlinear Systems Biology & Design (Sabin & Jones)
Kara Medow, Kirsten Shinnamon, Young-Suk Choi
Joshua Freese, Shuni Feng, Jeffrey Nesbit