A Model Microvasculature
Photo by Tom Cogill
From your body’s perspective, the microvasculature is where the action is. It is in these extremely tiny blood vessels at the very ends of our branching arteries and veins that the traffic in nutrients, waste products, and all manner of chemical signals occurs.
This microvasculature is dynamic. Exercise regularly, and the microvasculature blossoms, allowing more blood and nutrients to flow into muscles during exertion. When you are in shape, you can work harder without fatigue because your muscles have the support they need. Take a break from your routine, and before you know it your atrophying muscles will start sending signals to the local microvasculature and your capillaries will start to disappear. Next time you exercise, you’ll feel the lack of microvasculature.
“Understanding how the microvasculature remodels is critical to our ability to repair tissue and control disease,” says Shayn Peirce-Cottler, an assistant professor of biomedical engineering. Promoting the growth of the microvasculature could heal chronic wounds and help patients recover from heart attacks. Limiting its growth could prevent malignant tumors from growing and spreading.
Peirce-Cottler was named to Technology Review’s 2004 list of the world’s “100 Top Young Innovators” for developing highly refined computer models that allow scientists to visualize how the microvascular system responds to different stimuli. The models draw on rules of cellular behavior and integrate data from thousands of individual cells, including the endothelial cells and smooth muscle cells needed to build blood vessel walls. They also take into account the dynamic environment of the surrounding tissue, which influences the pace and direction of blood vessel construction. “My training in engineering is very helpful,” Peirce-Cottler says. “These models require a great deal of computing power and produce an enormous amount of data. As an engineer, I’m comfortable working with complex systems.”
With her colleagues, Peirce-Cottler demonstrated the potential of this model by using it to predict blood vessel growth in response to changes in blood pressure and the presence of a growth protein. Observations in the laboratory supported her results. “In computational systems biology, you’re always moving back and forth from the computer to the laboratory bench,” Peirce-Cottler says. “In fact, you get intimately acquainted with the biology when you do modeling, because you have to break down biological systems analytically and see if you can rebuild them in the simulation.”
At the same time, the results of her models help her think more critically about her experimental work. When there is a difference between what the model predicts and what she sees in the laboratory, the specific nature of the difference often suggests a new and productive line of research.
Peirce-Cottler is currently refining her models through her collaboration with Dr. Adam Katz, an assistant professor of plastic surgery. Katz is investigating the ability of human adipose-derived stem cells, collected during liposuction, to promote microvasculature growth and remodeling. Modeling is an important tool that helps guide this research.
Pierce-Cottler is also collaborating with two colleagues in her department, Assistant Professor Jason Papin and Professor Thomas Skalak, to build an even more ambitious model to study atherosclerosis, one that would integrate the metabolic, regulatory, and signaling networks within individual cells—Papin’s specialty—with the interactions among cells that has been her focus. “Spanning these different biological scales raises a number of complex issues for modeling,” she says. “If we succeed, we will have a very powerful way of pinpointing targets for drug discovery.”