CompuCell3D Simulations Reproduce Mesenchymal Cell Migration on Flat Substrates

Abstract

Mesenchymal cell crawling is a critical process in normal development, in tissue function, and in many diseases. Quantitatively predictive numerical simulations of cell crawling thus have multiple scientific, medical, and technological applications. However, we still lack a low-computational-cost approach to simulate mesenchymal three-dimensional (3D) cell crawling. Here, we develop a computationally tractable 3D model (implemented as a simulation in the CompuCell3D simulation environment) of mesenchymal cells crawling on a two-dimensional substrate. The F€ urth equation, the usual characterization of meansquared displacement (MSD) curves for migrating cells, describes a motion in which, for increasing time intervals, cell movement transitions from a ballistic to a diffusive regime. Recent experiments have shown that for very short time intervals, cells exhibit an additional fast diffusive regime. Our simulations' MSD curves reproduce the three experimentally observed temporal regimes, with fast diffusion for short time intervals, slow diffusion for long time intervals, and intermediate time -interval-ballistic motion. The resulting parameterization of the trajectories for both experiments and simulations allows the definition of time-and length scales that translate between computational and laboratory units. Rescaling by these scales allows direct quantitative comparisons among MSD curves and between velocity autocorrelation functions from experiments and simulations. Although our simulations replicate experimentally observed spontaneous symmetry breaking, short-timescale diffusive motion, and spontaneous cell-motion reorientation, their computational cost is low, allowing their use in multiscale virtual-tissue simulations. Comparisons between experimental and simulated cell motion support the hypothesis that short-time actomyosin dynamics affects longertime cell motility. The success of the base cell-migration simulation model suggests its future application in more complex situations, including chemotaxis, migration through complex 3D matrices, and collective cell motion.

Supracellular organization confers directionality and mechanical potency to migrating pairs of cardiopharyngeal progenitor cells

“…1F), suggesting that similar force distributions profiles may exist in both conditions. Cellular Potts Models or CPMs [32][33][34] and other types of models predict that cell morphologies emerge from the mechanical energies of diverse force-generating processes distributed within each cell (Fig. 1B).…”

“…Here, we model TVC shapes and behavior using the Cellular Potts Model (CPM) [32][33][34] . In the CPM framework, each cell is a shifting shape described by a sum of mechanical energies of cellsubstratum and cell-cell adhesions, surface tension and hydrostatic pressure, and protrusion and retraction forces (Fig.…”

“…The cell boundaries fluctuate, mimicking random forces and movements ubiquitous on sub-cellular scales, and shape changes minimizing the total energy are accepted, resulting in evolving, collectively moving cells (Supplemental Movies 1 and 2). While the CPM approach has some drawbacks, it is advantageous in modeling the TVC cell pair, as it allows us to reproduce both the detailed evolving 3D shapes of motile cells and the deformation of tissues surrounding these cells, over a reasonable computational time [32][33][34] -one of the more challenging tasks for detailed force-balance models in 3D 35 .…”

Fenômenos estocásticos em migração celular: teoria, experimentos e simulações

“…O modelo de simulação que discutimos nesta seção foi proposto por Fortuna e colaboradores [34]. Está baseado no modelo de Potts Celular [35][36][37] e foi realizado no ambiente Compucell3D [38].…”

PI3K inhibition reverses migratory direction of single cells but not cell groups in electric field

“…To the standard CPM, we added effective elastic coupling between neighboring cells and an effective force driving individual cells to or away from the cathode. Similar motile force was used in CPM before [44,52,53].…”