Mechanical and Thermodynamic Properties of Non-Muscle Contractile Tissues: The Myofibroblast and the Molecular Motor Non-Muscle Myosin Type IIA

Figures

• 

  Figure 1. Crossbridge NMIIA cycle. The NMIIA CB cycle is composed of six main successive conformational steps, of which three are detached (D1, D2, and D3) and three are attached (A1, A2, and A3); (a) In transition A3 ⟹ D1: ATP binds with the actin- non-muscle myosin (AM) complex, which induces myosin (M) detachment from actin (A). AM + ATP ⟹ A + M-ATP; (b) In transition D1 ⟹ D2: the ATP hydrolysis step leads to M—ATP ⟹ M-ADP-Pi. (c) In transition D2 ⟹ D3: M-ADP-Pi ⟹ M*-ADP-Pi; (d) In transition D3 ⟹ A1: this leads to the attachment state: M*-ADP-Pi binds with A: M*-ADP-Pi + A ⟹ AM-ADP-Pi; (e) In transition A1 ⟹ A2: the power stroke is triggered by the release of Pi: AM-ADP-Pi ⟹ AM-ADP + Pi. The power stroke generates a unitary CB force and a swing of the myosin CB; (f) Transition A2 ⟹A3: release of ADP according to AM-ADP ⟹ AM + ADP.

• 

  Figure 2. Hill hyperbolic tension (T)-velocity (V) relationship: The T-V hyperbolic relationship is established from a KCl-activated scaffold seeded with MSCs. Length (panel A) is progressively increased and tension (panel B) is progressively decreased by imposing several successive load clamps (LC). LC induces a brief transient overshoot. Maximum shortening velocity corresponding to a new isotonic load level is measured. (Panel C) represents the Hill hyperbolic T-V relationship. The curvature of the hyperbolic T-V relationship is introduced into Huxley’s equations to determine the molecular myosin properties (Table 1). This cardinal mechanical property is shared by both contractile muscles and non-muscle tissues.

• 

  Figure 3. Basic contractility of human placental stem villi. (Panels A and C): Effect of tetanic electrical stimulation on placental stem villi. (Panel A): placental villi shortening. (Panel C): tension. When the shortening of the placental stem villi reaches a plateau, its value is at its maximum. The arrow marks the time at which tension is suddenly increased by means of a load clamp, placing the placental villi under isometric conditions. Active tension is the difference between total isometric tension and resting passive basal tension (BT). (Panels B and D): Effect of 0.05 M KCl on placental villi. (Panel B): placental stem villi shortening length. (Panel D): tension.

• 

  Figure 4. Basic contractility of an MSC-seeded collagen scaffold. Effect of 0.05 M KCl on a MSC-laden collagen scaffold. (Panel A): scaffold shortening. (Panel B): tension generation. When the collagen scaffold reaches a plateau, shortening length reaches a maximum (maxSL). The black arrow marks the time at which tension is suddenly increased, placing the collagen scaffold under isometric conditions. Active tension (AT) is the difference between total isometric tension (TT) and resting passive tension (RT).

• 

  Figure 5. Frank-Starling mechanism. The Frank-Starling law indicates that when the initial length at rest (Lo) of the contractile sample increases, the active isometric tension also increases. The passive resting tension is measured in the presence of BDM, which inhibits the CB molecular motor interactions. Total isometric tension (TT in mN) is measured as a function of increasing initial length (Lo) of placental stem villi. Active isometric tension is the difference between total isometric tension and passive resting tension (RT) and increases when Lo increases. This cardinal mechanical property is shared by both contractile muscles and non-muscle contractile tissues.

• 

  Figure 6. Relaxation of human placental stem villi. When maximum shortening length is reached, relaxation is obtained by either decreasing the intracellular Ca2+ concentration (by addition of Sildenafil or ISDN in the bath) or by inhibition of myosin CB (by BDM or BLE). Relaxing effect of Sildenafil is shown on (panels A and B). Relaxing effect of ISDN is shown on (panels C and D). Isotonic relaxation is followed by isometric relaxation.