"There's a memory in each of these cells that helps define how they emerge into these very elaborate vasculature structures," she said. The cells that quickly differentiate into tip and stalk cells follow particular rules to advance, grow, divide and branch, depending on input from growth factors and from neighboring cells that can dictate how far and how fast they develop.
For instance, she said, in a chain of endothelial cells, a tip cell at its maximum length can only continue to migrate if the stalk cell immediately behind grows and pushes it forward. Similarly, the team set rules for branching and changes in direction, as well as an "idle" state, all based on observation of real vessel growth.
The researchers modeled a set of endothelial cells growing from a sphere and exposed them to simulated growth factors. They let them grow for what, in real life, would be a period of 24 hours, but in the computer took fractions of a second. They ran tens of thousands of simulations to see how the cells would migrate, proliferate and branch under various conditions.
The next step was to figure out which of the computer simulations matched actual behavior. Qutub's lab cultured spheres of human umbilical vein endothelial cells in collagen scaffolds, exposed them to growth factors and took microscope images as they developed networks over several days.
They compared these images with the simulations. The closest matches of which there are only a few amid thousands of simulations became the basis for a refined set of rules.
"We know how cells are connected as a function of the growth factors, and there are very distinct patterns to the way these
|Contact: David Ruth|