Creating your force regulatory model
You will construct three models in this chapter. These models are provided as sample models with model names tutorial Ca-F regulatory, tutorial SL dependent(0) and tutorial SL dependent(1).
Here you will include the force regulatory unit which responds to the calcium ion concentration [Ca2+] in its force generation. The actin filament is divided into segments which are referred as to the T/T units. Here the first and second “T”s represent the troponin and tropomyosin, respectively. The arrangement of the tropomyosin is controlled by the troponin that reacts with calcium ions and changes the configuration of tropomyosin to expose the biding sites. Here you will create the sarcomere model shown below by starting from the sample model tutorial energy aware MH-3.
The states of T/T units
There are two states in this T/T unit model. There is no calcium ion in the state Ca_off, whereas a calcium ion binds with the troponin in the state Ca_on. The transitions between the states are affected by the calcium ion concentration and the myosin heads below the T/T units. The XB Modeler can handle with these dependencies as described in Defining transitions of the T/T Units.
The states of myosin heads
In addition to the three states given in Toward energy-aware model, we define a no binding state N_XB. The state P_XB is also a no binding state in the sense that there in no contribution to the force generation. However, the myosin head in this state is close to the actin filament. Thus it is referred as to a weakly binding state. The transitions of a myosin head are affected by the T/T unit above it and the neighboring myosin heads. The XB Modeler can handle with these dependencies as described in Defining transitions with the cooperative behaviors of the Myosin Heads.
Defining T/T Unit states and modifying the myosin head model
Copying your model
Go to the Cell Models page in your dashboard and click on the Copy button on the row of the 3 state model made in Toward energy-aware model. Then a copy of the model appears on the top row. Click the Edit button.
Adding a no binding state to the three state model
Drag the state boxes downwards as shown below to give a space for placing a new state above them.
Click Add State. Then a new state box named S3 appears. Drag the new state box to right above the state box P_XB.
Click on the tentative state name S3 to define the no binding state N_XB. Then Click on the Select a type button to determine the type of N_XB. Select Nobinding from the radio buttons, and click on the Initial State check box. Checking the Initial State check box indicates that XB Modeler initializes states of all myosin heads with this state. Finally click on the Close button.
Erasing Initial State check from P_XB
Click on P_XB in the state box and then click on the Select a type button. Click on the check box of Initial State to erase the check from it. Then click on the Close button.
Click on again the tentative state name S3 to replace its name. Input a new state name N_XB in the text box. Click on the Rename button to finish renaming. Then you have finished the definition of the no binding state N_XB.
Defining T/T Unit states
Click on the T/T Unit tab to move the editing page of the T/T Unit. Click on the Add State button, then the state box with the tentative state name ST0 appears. Click on the Add State button again, then the state box with the tentative state name ST1 appears. Drag the second box as shown below.
Click on the tentative state name ST0, then click on the Select a type button. Click on the Initial State box to set this state as the initial state of the T/T units. Then click on the Close button. Click on again the tentative state name ST0 to replace its name. Input a new state name Ca_off in the text box. Click on the Rename button to finish renaming. Then you have finished the definition of the state Ca_off.
Click on the tentative state name ST1, then input a new state name Ca_on in the text box. Click on the Rename button to finish renaming. Then you have finished the definition of the state Ca_on.
