Fig 1.
Schematic representation of sarcomere.
(A). Sarcomeres are composed of thick and thin filaments that interact to generate force. Sarcomere length (SL) determines the length of single overlap region where cross-bridges (XB) can form and generate force. (B) At rest, the binding sites on the spherical actin are blocked by a strand of tropomyosin (Tm). Ca binding to Tn (TnCa) activates a troponin complex (Tn) resulting in the lateral movement of the Tm strand that unblocks the XB-binding sites. The Tn is composed of three subunits, troponin C (TnC), troponin I (TnI), and troponin T (TnT).
Fig 2.
Schematic representation of Tn activation.
(A) A RU is a functional unit of the sarcomere that is considered to work together. It is composed of 7 actin monomers, one tropomyosin (Tm) molecule, and one troponin complex (Tn). At rest, the C-terminal section of TnI extends over the actin monomer on the adjacent strand reaching to the Tm molecule, hindering its movement [17]. That hindrance is removed upon the conformational changes resulting from Ca2+ binding to that Tn. Note: Tn’s on adjacent actin strands are located in-register with one another, but this is not displayed in the figure. (B) A conformational change in the Tn caused by the binding of calcium to TnC effectively removes the Tm from the blocking position. (C) The thin filament in (A) is viewed from the longitudinal axis. The movement of Tm from the position blocking the XB-binding sites toward the groove reduces the radius (R) from the center of the actin double helix.
Fig 3.
Build-up of tension in the thin filament.
Each cross-bridge (XB) generates an individual force FXB. Tension S(x) at location x is the sum of each individual XB force from the start of the single overlap region closest to the mid line (x = 0) to the position x. So, tension along the thin filament increases with each XB exerting force.
Fig 4.
Static [Ca2+]-tension relationship in skinned muscle.
(A). The MechChem model generated [Ca2+]-tension relationship with all parameters fitted per curve. The dots on the curve are plotted from the data presented in Table 2 and Fig 2A of Dobesh et al. 2002 [18]. (B) Hill model generated [Ca2+]-tension curves. The experimental data points from Fig 4A were superimposed on the model generated curves. The error between the experimental data and both the (C) MechChem model generated [Ca2+]-tension curves and (D) the Hill model generated [Ca2+]-tension curves is shown.
Table 1.
Parameter values of fit model to experimental data.
Fig 5.
MechChem generated [Ca2+]-tension relationship in skinned muscle.
The MechChem model generated [Ca2+]-tension relationship with KTnCa0 changing with SL, while setting Cf = 1.93∙106 m-1S and Cs = 6.5 S-1. The unit S refers to the unit of tension as shown by Dobesh et al. [18]. The dots on the curve are plotted from the data presented in Table 2 and Fig 2A of Dobesh et al. 2002 [18].
Fig 6.
Tension and the proportion of activated troponin complexes (Tn) P(x) in the thin filament along the single overlap region.
A sarcomere with length 2.05 μm was modeled with constant calcium concentrations ([Ca]). The blue, purple, and magenta lines represent a [Ca] of 3, 4, and 5 μM, respectively. (A) The plot shows the non-linear cumulative tension developed at position x along the single overlap region. (B) P(x) is displayed. The plateaus reached at [Ca]’s of 4 and 5 μM represent the full activation of Tn’s, i.e. all binding sites on that section of the thin filament are exposed for XB binding.