TOPAS-Tissue: A Framework for the Simulation of the Biological Response to Ionizing Radiation at the Multi-Cellular...

Area of Science:

• Computational Biology
• Radiation Physics
• Biophysics

Background:

• Simulating cellular response to ionizing radiation requires integrating physical and biological processes across multiple scales.
• Existing models often lack the capability to link radiation transport and chemistry with detailed cellular behavior and population dynamics.

Purpose of the Study:

• To develop and validate TOPAS-Tissue, a novel multiscale simulation framework for modeling the biological response of cell populations to ionizing radiation.
• To couple the Monte Carlo (MC) code TOPAS with the agent-based model CompuCell3D for an end-to-end simulation of radiation effects.

Main Methods:

• Coupled TOPAS (with TOPAS-nBio) for track-structure and chemistry simulation with CompuCell3D for agent-based cell modeling.
• Simulated a 2-D PC-3 cell culture clonogenic survival assay irradiated with MV X-rays (0-8 Gy).
• Incorporated models for DNA double-strand break (DSB) induction, repair (two-lesion kinetic model), and cell response (p53 pulse model).

Main Results:

• The simulated cell survival curve exhibited a linear-quadratic dose response.
• Fitted coefficients (α = 0.280 ± 0.025/Gy, β = 0.042 ± 0.006/Gy²) closely matched published experimental data.
• Demonstrated successful end-to-end simulation from irradiation and DNA damage to cell fate in a population.

Conclusions:

• TOPAS-Tissue provides an extensible, all-in-one simulation framework for multiscale biological response to radiation.
• The framework successfully integrates CompuCell3D and TOPAS, enabling comprehensive simulations of radiation effects on cell populations.
• This approach advances the understanding of radiation biology by linking physical interactions to cellular outcomes.