Pulmonary hypertension is an incurable disease characterized by increased blood pressure within the lung, leading to heart failure. At the level of the blood vessel wall and with pulmonary hypertension, smooth muscle cells that line and reinforce these structures, move from their usual resting place into the lumen of the vessel, leading to vessel occlusion. In order to do this, the cells use enzymes to break down their surrounding collagen extracellular matrix, and respond to this degraded microenvironment by changing their motile behavior as an attempt to repair the blood vessel wall. Understanding how smooth muscle cells respond to normal or degraded collagen may therefore provide new ways of understanding and ultimately treating this disease. To model these behaviors, we have examined real-time movies of pulmonary artery vascular smooth muscle cells cultivated on native or denatured collagen. Thereafter, we abstracted these behaviors into digital and fabricated design environments, based on newly devised rule sets. Overall, the furthest reach and direction of motility differed between native and denatured collagen, as did cell growth. One analysis looked at the overall scale of the cell by examining the relationship between the nucleus and the furthest extension of lamelliopodia or filopodia. Cells on denatured collagen also appeared to have increased growth rates. To describe and simplify these behaviors, a series of circles with a center at the nucleus and radius to the furthest reach, a simulation of various cell behaviors can be utilized to mimic cell behavior. Initial variables considered were motility: motile, little movement, and non-moving and growth: consistent growth, fluctuating growth, and non-growing, which in combination was used to depict differentiated cell behavior. Supplementary, connections between the cells will be made illustrating association and gathering as well as be used to represent the extracellular matrix. Considerations for the connections include fixed connections, between same-cells, and flexible, between different corresponding cells.
UPenn Dept of ARCH745, Nonlinear Systems Biology & Design (Sabin & Jones)
Jared Bledsoe, Vahit K Muskara, Gillian Stoneback