Accessing radiation damage to biomolecules on the nanoscale by particle-scattering simulations

Abstract

Radiation damage to DNA plays a central role in radiation therapy to cure cancer. The physico-chemical and biological processes involved encompass huge time and spatial scales. To obtain a comprehensive understanding on the nano and the macro scale is a very challenging tasks for experimental techniques alone. Therefore particle-scattering simulations are often applied to complement measurements and aide their interpretation, to help in the planning of experiments, to predict their outcome and to test damage models. In the last years, powerful multipurpose particle-scattering framework based on the Monte-Carlo simulation (MCS) method, such as Geant4 and Geant4-DNA, were extended by user friendly interfaces such as TOPAS and TOPAS-nBio. This shifts their applicability from the realm of dedicated specialists to a broader range of scientists. In the present review we aim to give an overview over MCS based approaches to understand radiation interaction on a broad scale, ranging from cancerous tissue, cells and their organelles including the nucleus, mitochondria and membranes, over radiosensitizer such as metallic nanoparticles, and water with additional radical scavenger, down to isolated biomolecules in the form of DNA, RNA, proteins and DNA-protein complexes. Hereby the degradation of biomolecules by direct damage from inelastic scattering processes during the physical stage, and the indirect damage caused by radicals during the chemical stage as well as some parts of the early biological response is covered. Due to their high abundance the action of hydroxyl radicals (•OH) and secondary low energy electrons (LEE) as well as prehydrated electrons are covered in additional detail. Applications in the prediction of DNA damage, DNA repair processes, cell survival and apoptosis, influence of radiosensitizer on the dose distribution within cells an their organelles, the study of linear-energy-transfer (LET), the relative-biological-effectiveness (RBE), ion-beam cancer-therapy, microbeam-radiation-therapy (MRT), the FLASH effect, and the radiation induced bystander effect are reviewed.

Monte Carlo Simulation of Electron Interactions in an MeV-STEM for Thick Frozen Biological Sample Imaging

“…It is commonly used to estimate the probability of different outcomes in a process [23][24][25]. In radiation therapy to cure cancers, MC simulation-based methods have been employed to study the degradation of biomolecules by direct damage from inelastic scattering processes (most primary particles have initial energies in the MeV range) [26]. The track structure and properties of energy deposition and dose distributions have been estimated.…”

Condensed Matter Systems Exposed to Radiation: Multiscale Theory, Simulations, and Experiment

“…Further details on the utilization of the MC method for simulating particle transport in biologically relevant media can be found, e.g. , in refs , , and and references therein. Some of the MC codes ( e.g.…”

Optimize Electron Beam Energy toward In Situ Imaging of Thick Frozen Bio-Samples with Nanometer Resolution Using MeV-STEM

“…We benchmarked the beam size as a function of sample thickness predicted by the analytical model via a recently implemented MC simulation code [11,[27][28][29][30][31][32] since in the study presented in this manuscript, accurately modelling inelastic scattering events in addition to elastic scattering events is extremely important, especially in such a low electron beam energy regime, ranging from a few hundred kilo-electron-volts to tens mega-electronvolts. Precisely calculating the differential scattering cross-section of electrons in amorphous ice to align with experimental observations is not so straightforward (see Section 2.1); thus, we implemented a new Monte Carlo code [11] for the purpose of precisely controlling parameters used to model inelastic scattering events in amorphous ice.…”