IMC Colloquium Series: "Applications for a 3-D, individual cell based model of cell movement and visualization in multicellular systems, fashioned on mechanical and chemical cell interactions"

Abstract

A three-dimensional mathematical model was developed to explore by simulation and visualization how cell signaling, adhesion, motility, and stiffness affect cell movements and growth in multicellular systems. Here I show the ramifications of these interactions for a number of different biological systems and demonstrate that the emerging cell patterns in these multicellular systems are distinctively different from that of an individual cell. The building blocks of the model are individual deformable ellipsoidal cells, where the cell response, both mechanical and chemical, depends on its internal parameter state (cell adhesion and stiffness) and on external cues from the neighboring cells, extracellular matrix, and chemical signals. Cell movement and deformation is then calculated from the equations of motion using the total force acting on each cell, ensuring that forces are balanced. The model uses experimentally measured cellular characteristics, can simulate over 100,000 cells, and is adaptable to many different systems. I will show simulations of cell movements and cell signaling in Dictyostelium discoideum and explore cell sorting and chemotaxis. Simulations of paracrine signaling interactions between macrophages and tumor cells show how these interactions facilitate tumor cell invasion. Finally, I will show examples of how the model can be used to model tumor growth and cell metastasis.