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Agent-based model for microbial populations exposed to radiation (AMMPER) simulates yeast growth for deep-space experiments

Gravitational and Space Research
Volume 12 (2024): Issue 1 (January 2024)
By:
Open Access
|Nov 2024

Figures & Tables

Figure 1.

RITRACKS energy depositions [33]. Data generated from RITRACKS representing the energy depositions of a proton traversal, which passes through the point (0,0,0) and is oriented along the Y axis. (a) Cross-sectional view of proton traversal energy depositions. The density of electron energy depositions, indicated by the white dots, decreases radially further away from the proton traversal. (b) 3D view of energy depositions. Energy depositions (white dots) occur along linear proton traversal, and the radius of the track is small.
RITRACKS energy depositions [33]. Data generated from RITRACKS representing the energy depositions of a proton traversal, which passes through the point (0,0,0) and is oriented along the Y axis. (a) Cross-sectional view of proton traversal energy depositions. The density of electron energy depositions, indicated by the white dots, decreases radially further away from the proton traversal. (b) 3D view of energy depositions. Energy depositions (white dots) occur along linear proton traversal, and the radius of the track is small.

Figure 2.

Block diagram of AMMPER. AMMPER integrates a model of radiation energy deposition with algorithms for population growth, cell damage, and DNA repair, and is parameterized with experimental data.
Block diagram of AMMPER. AMMPER integrates a model of radiation energy deposition with algorithms for population growth, cell damage, and DNA repair, and is parameterized with experimental data.

Figure 3.

Model cell spatial definition. A cell is represented by the red sphere with a diameter of 4 μm, inscribed inside a 4×4×4 μm cubic space (shown on the left, with each blue cube having dimensions of 1×1×1 μm). Each cell exists in a neighborhood (shown on the right, with each larger blue cube having dimensions of the 4×4×4 μm volume that holds a single cell), which consists of all 26 cell spaces bordering the cell’s cubic space.
Model cell spatial definition. A cell is represented by the red sphere with a diameter of 4 μm, inscribed inside a 4×4×4 μm cubic space (shown on the left, with each blue cube having dimensions of 1×1×1 μm). Each cell exists in a neighborhood (shown on the right, with each larger blue cube having dimensions of the 4×4×4 μm volume that holds a single cell), which consists of all 26 cell spaces bordering the cell’s cubic space.

Figure 4.

PNG images generated by AMMPER code as a product of the simulation run, showing three different radiation environments. Each simulation produces one PNG image file per generation; generation number is noted at the top as “g=”. Yellow dots represent energy depositions from protons and electrons, green dots represent ROS produced in the ionization of water molecules, and blue dots represent the cells in the simulation space. For all simulations, a cell is placed in the center of the cubic simulation space and undergoes exponential growth. (a) Deep Space Proton: The proton traversals are omnidirectional, and the timing of each proton is staggered to produce an environment that simulates the constant radiation exposure of deep space. Generation 11 shown here. Total dose delivered is 4.49 mGy in a 3-day simulation. (b) NSRL GCRSim Proton: All radiation is delivered at Generation 2, shown here. Proton traversals are parallel, and the total dose simulates the dose of a year of deep space radiation (1.19 Gy). (c) 150 MeV Proton, 10 Gy: All radiation is delivered at Generation 2, shown here. Total dose delivered is 10 Gy.
PNG images generated by AMMPER code as a product of the simulation run, showing three different radiation environments. Each simulation produces one PNG image file per generation; generation number is noted at the top as “g=”. Yellow dots represent energy depositions from protons and electrons, green dots represent ROS produced in the ionization of water molecules, and blue dots represent the cells in the simulation space. For all simulations, a cell is placed in the center of the cubic simulation space and undergoes exponential growth. (a) Deep Space Proton: The proton traversals are omnidirectional, and the timing of each proton is staggered to produce an environment that simulates the constant radiation exposure of deep space. Generation 11 shown here. Total dose delivered is 4.49 mGy in a 3-day simulation. (b) NSRL GCRSim Proton: All radiation is delivered at Generation 2, shown here. Proton traversals are parallel, and the total dose simulates the dose of a year of deep space radiation (1.19 Gy). (c) 150 MeV Proton, 10 Gy: All radiation is delivered at Generation 2, shown here. Total dose delivered is 10 Gy.

Figure 5.

Distribution of RITRACKS ion and electron energy depositions. (a) Energy deposition in a single cell volume for radiation due to proton traversals of various energies. The RITRACKS data are depicted in yellow, and the microdosimetry-based calculations depicted in green. (b) Energy depositions by a 1 MeV proton. Light blue dots and line show energy depositions from delta rays, generated by RITRACKS, as a function of radial distance. Dark blue dots show Wingate and Baum experimental data on energy deposited by a 1 MeV proton in tissue-equivalent gas as a function of radial distance [46]. As distance from the proton track increases, the amount of energy deposited decreases.
Distribution of RITRACKS ion and electron energy depositions. (a) Energy deposition in a single cell volume for radiation due to proton traversals of various energies. The RITRACKS data are depicted in yellow, and the microdosimetry-based calculations depicted in green. (b) Energy depositions by a 1 MeV proton. Light blue dots and line show energy depositions from delta rays, generated by RITRACKS, as a function of radial distance. Dark blue dots show Wingate and Baum experimental data on energy deposited by a 1 MeV proton in tissue-equivalent gas as a function of radial distance [46]. As distance from the proton track increases, the amount of energy deposited decreases.

Figure 6.

One of the PNG images generated by AMMPER code as a product of the simulation run, showing ROS species generation for the NSRL GCRSim proton simulation in AMMPER. ROS species are shown as green dots; each point corresponds to a single molecule of either OH· or H2O2. ROS species are generated due to the ionization of water molecules by the energy depositions from the ions of the radiation tracks.
One of the PNG images generated by AMMPER code as a product of the simulation run, showing ROS species generation for the NSRL GCRSim proton simulation in AMMPER. ROS species are shown as green dots; each point corresponds to a single molecule of either OH· or H2O2. ROS species are generated due to the ionization of water molecules by the energy depositions from the ions of the radiation tracks.

Figure 7.

Comparison between cell survival for long and short ROS models. Simulations were initiated with 1 cell per 64×64×64 μm cubic volume. Total radiation dose in Gy is depicted along the x axis. The circles represent the number of dead cells in the long ROS model, whereas the diamonds represent those in the short ROS model. Note that damaged cells are not included. Each symbol represents one model replicate. (a) Wild-type simulated data. Circles and diamonds lie on top of each other; no cell death was observed in either ROS model. (b) rad51Δ simulated data.
Comparison between cell survival for long and short ROS models. Simulations were initiated with 1 cell per 64×64×64 μm cubic volume. Total radiation dose in Gy is depicted along the x axis. The circles represent the number of dead cells in the long ROS model, whereas the diamonds represent those in the short ROS model. Note that damaged cells are not included. Each symbol represents one model replicate. (a) Wild-type simulated data. Circles and diamonds lie on top of each other; no cell death was observed in either ROS model. (b) rad51Δ simulated data.

Figure 8.

Comparison between empirical and simulated log phase growth rates. Radiation dose in Gy is depicted along the x axis. The open triangles represent the data from AMMPER, and the filled squares represent the empirical data. Each symbol represents one replicate (3 replicates/dose level for empirical and model data), and the error bars represent the linear regression fit error. Colors match the color codes in Figure S2. (a) wild-type empirical data; (b) wild-type simulated data; (c) rad51Δ empirical data; (d) rad51Δ simulated data.
Comparison between empirical and simulated log phase growth rates. Radiation dose in Gy is depicted along the x axis. The open triangles represent the data from AMMPER, and the filled squares represent the empirical data. Each symbol represents one replicate (3 replicates/dose level for empirical and model data), and the error bars represent the linear regression fit error. Colors match the color codes in Figure S2. (a) wild-type empirical data; (b) wild-type simulated data; (c) rad51Δ empirical data; (d) rad51Δ simulated data.

Figure 9.

Comparison between empirical and simulated lag time. Radiation dose in Gy is depicted along the x axis. The open triangles represent the data from AMMPER, and the filled squares represent the empirical data. Each symbol represents one replicate (3 replicates per dose for both empirical and model data), and the error bars represent the error in the linear regression fit. Colors match the color codes in Figure S2. (a) wild type empirical data; (b) wild type simulated data; (c) rad51Δ empirical data; (d) rad51Δ simulated data.
Comparison between empirical and simulated lag time. Radiation dose in Gy is depicted along the x axis. The open triangles represent the data from AMMPER, and the filled squares represent the empirical data. Each symbol represents one replicate (3 replicates per dose for both empirical and model data), and the error bars represent the error in the linear regression fit. Colors match the color codes in Figure S2. (a) wild type empirical data; (b) wild type simulated data; (c) rad51Δ empirical data; (d) rad51Δ simulated data.

Figure 10.

Log phase growth rate for deep space proton and NSRL GCRSim proton simulations. Error bars represent the error in the linear regression fit. Dark blue, gray, and light blue represent the three replicates. noRad = control simulation without radiation, both strains (6 points). wt = wild type S. cerevisiae. rad51 = rad51Δ mutant. (a) Deep space proton simulation. There is minimal difference among the growth rates, regardless of modeled cell strain and radiation level. (b) NSRL GCRSim proton simulation. Growth rate is higher in wild-type cells exposed to radiation, and lower in rad51Δ cells exposed to radiation.
Log phase growth rate for deep space proton and NSRL GCRSim proton simulations. Error bars represent the error in the linear regression fit. Dark blue, gray, and light blue represent the three replicates. noRad = control simulation without radiation, both strains (6 points). wt = wild type S. cerevisiae. rad51 = rad51Δ mutant. (a) Deep space proton simulation. There is minimal difference among the growth rates, regardless of modeled cell strain and radiation level. (b) NSRL GCRSim proton simulation. Growth rate is higher in wild-type cells exposed to radiation, and lower in rad51Δ cells exposed to radiation.

Summary of parameters used in AMMPER_

ParameterSourceValueNotes
Yeast populationCell density at model initiationMimics experimental design3.85×106 cells/mL = 1 cell per 2.5974×105 µm3
Yeast baseline growth rateFit from empirical dataGeneration time = 5 hoursCalculated from WT 0 Gy growth curve, then used to correlate model time (1 timestep = 1 generation) to real time (hours)
Yeast cell volumeJorgensen et al., 2007 [38]33.51 µm3
Yeast nucleus volume7% of cell volume
Yeast genotypesSanta Maria et al., 2020 [19]; Liddell et al. 2023 [28]Wild type and rad51Δ. Identical, except that in AMMPER, rad51Δ is incapable of any DNA repair.The lack of DNA repair capability is a simplification for AMMPER. See references for more complete descriptions.
Simulated volume150 MeV Proton and GCRSim Proton scenariosDetermined by computational resources available64×64×64 µmThese values could be increased for simulation on higher-powered computers
Deep Space Proton scenario300×300×300 µm
Simulation duration15 generations (75 hours, 3.125 days)
Radiation dose rate, timing, geometry150 MeV proton scenarioMimics experimental design0, 2.5, 5, 10, 20, 30 Gy; unidirectional 150 MeV protons only; single event at Generation 2See Table S3 for detail
Deep Space Proton scenarioSimonsen et al., 2020 [42]4.49 mGy; omnidirectional protons ranging in energy from 42.76 to 120.35 MeV; evenly spaced over 3 daysSee Table S1 for detail
GCRSim Proton scenarioKim et al., 2015 [44]; Simonsen et al., 2020 [42]1.19 Gy; unidirectional protons ranging in energy from 20 to 1000 MeV; single event at Generation 2See Table S2 for detail
Radiation track structure and energy deposition per protonPlante & Wu, 2014 [35]RITRACKS model output
ROSOH· generation ratePlante, 20212.5 molecules/100 eV per voxelThis value is for ROS generation in water; AMMPER does not take medium composition into account
H2O2 generation ratePlante, 20210.7 molecules/100 eV per voxel
ROS lifetimeinformed by empirical datano half-life: all ROS generated persists in the modelROS lifetime was not fit to data, but long ROS was chosen over short ROS to achieve a qualitative match to observations of dose-dependent effects on growth rate
DNA damage ratesSSBs, direct (from radiation)Cucinotta et al., 1996 [53]; Nikjoo et al., 1999 [54]1 SSB per electron energy deposition
DSBs, direct (from radiation)Erixon et al., 1995 [55]; Ponomarev et al., 2012 [56]35 DSBs/cell/Gy
SSBs, indirect (from ROS)unique to the modelone SSB per OH· molecule
Probability of apoptosis from ROSMadeo et al., 1999 [57]20% at 0.3 mM H2O2, 40% at 1 mM H2O2, 70% at 3 mM H2O2, 0% at 5 mM H2O2, extrapolated linearly between those points
Health statusunique to the modelany SSBs or DSBs → health status 2 = “damaged.” apoptosis → health status 3 = “dead”
DNA repair rate“simple”Lettier et al., 2006 [61]3 SSBs per generation, probability of success 100%Repair rate and probability of success was simplified from literature to fit AMMPER model format
“complex”1 DSP per generation, probability of success 50%
DOI: https://doi.org/10.2478/gsr-2024-0012 | Journal eISSN: 2332-7774
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Language: English
Page range: 159 - 176
Published on: Nov 23, 2024
Published by: American Society for Gravitational and Space Research
In partnership with: Paradigm Publishing Services
Publication frequency: 2 times per year
Keywords:
radiation biology,
mutant yeast strains,
agent-based modeling
Related subjects:
Life sciences,
Life sciences, other,
Materials sciences,
Materials sciences, other,
Physics,
Physics, other

© 2024 Amrita Singh, Sergio R. Santa Maria, Diana M. Gentry, Lauren C. Liddell, Matthew P. Lera, Jessica A. Lee, published by American Society for Gravitational and Space Research
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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