Multicellular Sprouting In Vitro

Abstract

Cell motility and its guidance through cell-cell contacts is instrumental in vasculogenesis and in other developmental or pathological processes as well. During vasculogenesis, multicellular sprouts invade rapidly into avascular areas, eventually creating a polygonal pattern. Sprout elongation, in turn, depends on a continuous supply of endothelial cells, streaming along the sprout toward its tip. As long-term videomicroscopy of in vitro cell cultures reveal, cell lines such as C6 gliomas or 3T3 fibroblasts form multicellular linear arrangements in vitro, similar to the multicellular vasculogenic sprouts. We show evidence that close contact with elongated cells enhances and guides cell motility. To model the patterning process we augmented the widely used cellular Potts model with an inherently nonequilibrium interaction whereby surfaces of elongated cells become more preferred adhesion substrates than surfaces of well-spread, isotropic cells.

Modeling Morphogenesisin silicoandin vitro: Towards Quantitative, Predictive, Cell-based Modeling

“…Szabo and coworkers [52,51] observed that non-vascular (glia-and muscle related) cells can form irregular networks on rigid tissue culture substrates with continuously shaken culture medium, hence excluding traction-based or chemotaxis-based patterning mechanisms. Instead they proposed that cells are preferentially attracted to locally elongated configurations of cells [52] , or that cells adhere most strongly to elongated cells [51].…”

“…Instead they proposed that cells are preferentially attracted to locally elongated configurations of cells [52] , or that cells adhere most strongly to elongated cells [51]. This mechanism produces vascular-like network patterns (Fig.…”

“…D. Overdamped chemotactic motion of round endothelial cells with contact-inhibition of motility. E and F. Preferential attraction to elongated cellular configurations [52,51]. Panel E reprinted with permission from Ref.…”

Cell-Based Computational Modeling of Vascular Morphogenesis Using Tissue Simulation Toolkit

“…This makes it possible to study in a simulation model how the behavior of the individual cells is responsible for the collective. Such cell-based models, more in particular the Cellular Potts model [12], have, e.g., shown how cell shape changes the collective behavior of aggregating cells from spheroid aggregates to network patterns [13,14], studied the role of contact-inhibition in collective endothelial cell behavior [15], and showed that preferential attraction to elongated cells mediates the formation of vascular networks [16]. Such models are easily extended to model the interactions of cells and growth factors with the microenvironment, including the extracellular matrix [17][18][19].…”

“…Thus, if you intend to use standard, cellular Potts technology and want to develop three-dimensional simulations, CompuCell3D is your package. If you want to develop new CPM technology, e.g., experiment with the Cellular Potts algorithm [16,31], add new Hamiltonian components [19], run large parameter sweeps [15], or build novel hybrid models [32] this is certainly possible using CompuCell3D [14,21]. CompuCell3D is well extensible, but its size and complexity can make it hard to keep the overview, and to quickly experiment with alternative algorithms, model set ups, new Hamiltonians, and so forth.…”