Konstantinopoulos, K. | Search bioRxiv

bioRxiv2022

PhysiCell training apps: Cloud hosted open-source apps to learn cell-based simulation software

Cell-based tissue simulations require not only the ability to write new code in a simulation framework, but also an understanding of underlying mathematical models, background biology, and parameters for each behavior of an agent. This can entail a steep learning curve for interdisciplinary researchers joining computational biology research. We have created a suite of cloud-hosted open-source tools to separately explore and learn key components of an agent-based cellular simulation framework. This creates an self-contained environment to learn and test functions of cells and the micro-environment in a modular fashion before creating more detailed, research-focused simulation models.

systems biology↗

bioRxiv2021

A persistent invasive phenotype in post-hypoxic tumor cells is revealed by novel fate-mapping and computational modeling

Hypoxia is a critical factor in solid tumors that has been associated with cancer progression and aggressiveness. We recently developed a hypoxia-fate mapping system that allowed the tracing of post-hypoxic cells within a tumor for the first time. This novel approach, based on an oxygen-dependent fluorescent switch, made the investigation of the post-hypoxic phenotype possible. The system allowed us to measure key biological features such as oxygen distribution, cell proliferation and migration. Using this data, we developed a computational model to investigate the motility and phenotypic persistence of hypoxic and post-hypoxic cells during tumor progression. The behavior of hypoxic and post-hypoxic cells was defined by phenotypic persistence time, cell movement bias and the fraction of cells that respond to an enhanced migratory stimulus. Our studies revealed that post-hypoxic cells have an enhanced persistent migratory phenotype that promotes the formation of invasive structures ("plumes") expanding towards the oxygenated tumor regions. This work combined advanced cell tracking and imaging techniques with mathematical modeling, and revealed for the first time that a persistent invasive migratory phenotype that develops under hypoxic conditions enhances their escape into non-hypoxic tumor regions to invade the surrounding tissue.

cancer biology↗