Fig 1.
Schematic representation of a model cell.
rN, rC are the nuclear and cellular radius, respectively. In the cytoplasm (rN < r < rC), Gag monomers can aggregate to dimers, but not higher-order polymers. Monomers and dimers are transported actively by molecular motors along microtubules and can diffuse along the direction of the concentration gradient. Underneath the plasma membrane (rC), monomers can be polymerized to hexamers.
Table 1.
Nomenclature of the mathematical symbols.
Fig 2.
A cartoon to show the polymerization reaction of a monomer and a pentamer.
Table 2.
Polymerization reactions and statistical factors.
Table 3.
Some parameter values estimated by the experimentally measured data.
Fig 3.
The flow chart of the parameter optimization.
Fig 4.
Comparisons between the simulation results and experimental data.
Gagi(i = 1, 2, ⋯, 6) denotes a polymer with i monomers. The subfigure on the left illustrates the comparisons between the simulation and experimental results for Gag monomers and dimers in the cytoplasm. The subfigure on the right shows the differences between the simulation and experimental results for the six types of polymers at the plasma membrane. The concentration of each polymer was normalized by dividing by the concentration of Gag monomer in the cytoplasm.
Table 4.
Some parameter values for WT Gag optimized by the Tikhonov regularization method with data from [10].
Fig 5.
Comparison between the simulation results and experimental data for Gag-G2A.
Gagi(i = 1, 2, ⋯, 6) denotes a polymer with i monomers. The left side illustrates the comparisons between the simulation and experimentally measured concentrations for monomers and dimers in the cytoplasm. The right side shows the differences between the simulation and experimentally measured concentrations with the six types of polymers at the plasma membrane. The concentration of each type of polymer was normalized by dividing by the concentration of Gag monomer in the cytoplasm.
Fig 6.
Blue lines display the profile likelihood for the parameter.
The vertical dashed lines indicate the optimal values of the parameters shown in Table 4. Each parameter was varied over a wide range around its optimal value, and the remaining parameters were then refitted. All parameter values were log-transformed.
Fig 7.
Comparison between the simulation results and experimental data for Gag-dCTD.
Gagi(i = 1, 2, ⋯, 6) denotes a polymer with i monomers. The subfigure on the left side illustrates the comparisons between the simulation and experiment concentrations for monomers and dimers in the cytoplasm. The subfigure on the right side shows the differences between the simulation and experiment concentrations for the six types of polymers at the plasma membrane. The concentration of each polymer was normalized by dividing by the concentration of Gag monomer in the cytoplasm.
Table 5.
Values of some parameters for Gag-dCTD.
Fig 8.
Elasticity analysis of parameters corresponding to eight types of polymers.
Gi(i = 1, 2, ⋯, 6) denotes a polymer with i monomers at the plasma membrane. P1 and P2 indicate the monomer and dimer concentrations in the cytoplasm, respectively.
Fig 9.
The global elasticity analysis of the parameters.
Fig 10.
The contributions of three pathways to form hexamers.
Fig 11.
The contributions of two pathways to form pentamers.
Fig 12.
The contributions of two pathways to form tetramers.
Table 6.
Compare the concentrations of higher-order polymers 1.
Fig 13.
Concentration of polymers in the cytoplasm and PM during the first 30 minutes of simulations using the four theoretical combined methods and WT Gag.
Gagi(i = 1, 2, ⋯, 6) denotes a polymer with i monomers.