Computational Models of Vascularization and Therapy in Tumor Growth - Mechanical and Chemical Signaling in Angiogenesis - page 234

Fig. 6 Schematic view of the multiscale model as proposed in [ 56 ]

identical to vascular beds formed in vivo by vasculogenesis. This phenomenon has
been called in vitro angiogenesis or in vitro vasculogenesis [ 67 ].
In the experiments we discuss here, a Petri dish is coated with an amount of
Matrigel, a natural basal membrane matrix which favours cell motility and has
biochemical characteristics similar to living tissues. Human endothelial cells from
large veins or adrenal cortex capillaries (HUVEC), or other similar types of cells,
sediment onto the Matrigel surface from the physiological solution above. Cells
then move on the horizontal surface, giving rise to a process of aggregation and
pattern formation. The evolution of the process is the following: In the first 3-6 h
endothelial cells migrate independently, keeping a round shape till they collide
with closest neighbors. The cells eventually form a continuous multicellular net-
work and adhere more strongly on the Matrigel multiplying the number of
adhesion sites. Because of the increased number of activated adhesion sites, the
network then slowly moves as a whole, undergoing a slow thinning process, while
still leaving the network structure mainly unaltered. Finally, at the end of the
process after nearly 20 h, individual cells fold up to form the lumen of the cap-
illary, so that one has the formation of a capillary-like network along the lines of
the previously formed two-dimensional structure.
Focusing on the trajectories of single cells, in most cases the direction of
motion is well established and kept till the cells encounter other cells. Of course, a
random component is present but is usually not predominant. The trajectories of
individual cells then show what is usually called a degree of persistence in the
direction of cell motion, i.e., a tendency to maintain its own direction of motion. In
addition, in most cases the motion is apparently directed toward zones of higher
concentration of cells, which suggests the presence of a mechanism of cross-talk
among cells mediated by a protein secreted by the endothelial cells themselves.