Role of time dependent single cell stiffness change in collective behavior of tumor invasion

Cell migration plays an essential role in wound healing, tumor invasion, and organ formation during embryo development. While the biochemical factors that support cell migration is comparatively well studied, the effect of physical forces on cell migration needs to be better understood. A physics-based description of cell migration could pave the way towards an improved means of controlling tumor invasion and metastasis. Using computational modeling of cell collectives, we investigate the migration of cancer cells in tumor spheroids during initial stages of tumor growth. Using a three-dimensional model incorporating cell birth, cell death and physical interactions based on cell stiffness and adhesion, we study the impact of time dependent single cell stiffness change on tumor growth and invasiveness. We track and compute how individual cell displacement impacts the temporal evolution of tumor size. We also quantify how spatial patterns in cell stiffness affects tumor spreading. We conclude that time dependent cancer cell stiffness, with enhanced cell stiffness prior to division and softening after division driven by actin build up and decay, leads to heightened cell dynamics and increased tumor size. In comparison, tumors with cells that do not soften in stiffness after cell division leads to more restricted cell dynamics and tumor size growth.