Energy Transduction In Muscle Research Articles

The Synergic Role of Actomyosin Architecture and Biased Detachment in Muscle Energetics: Insights in Cross Bridge Mechanism beyond the Lever-Arm Swing

Muscle energetics reflects the ability of myosin motors to convert chemical energy into mechanical energy. How this process takes place remains one of the most elusive questions in the field. Here, we combined experimental measurements of in vitro sliding velocity based on DNA-origami built filaments carrying myosins with different lever arm length and Monte Carlo simulations based on a model which accounts for three basic components: (i) the geometrical hindrance, (ii) the mechano-sensing mechanism, and (iii) the biased kinetics for stretched or compressed motors. The model simulations showed that the geometrical hindrance due to acto-myosin spatial mismatching and the preferential detachment of compressed motors are synergic in generating the rapid increase in the ATP-ase rate from isometric to moderate velocities of contraction, thus acting as an energy-conservation strategy in muscle contraction. The velocity measurements on a DNA-origami filament that preserves the motors’ distribution showed that geometrical hindrance and biased detachment generate a non-zero sliding velocity even without rotation of the myosin lever-arm, which is widely recognized as the basic event in muscle contraction. Because biased detachment is a mechanism for the rectification of thermal fluctuations, in the Brownian-ratchet framework, we predict that it requires a non-negligible amount of energy to preserve the second law of thermodynamics. Taken together, our theoretical and experimental results elucidate less considered components in the chemo-mechanical energy transduction in muscle.

A closer look at energy transduction in muscle.

Muscular force is the sum of unitary force interactions generated as filaments of myosins move forcibly along parallel filaments of actins, understanding that the free energy required comes from myosin-catalyzed ATP hydrolysis. Using results from conventional biochemistry, our own mutational studies, and diffraction images from others, we attempt, in molecular detail, an account of a unitary interaction, i.e., what happens after a traveling myosin head, bearing an ADP-P(i), reaches the next station of an actin filament in its path. We first construct a reasonable model of the myosin head and actin regions that meet to form the "weakly bound state". Separately, we consider Holmes' model of the rigor state [Holmes, K. C., Angert, I., Kull, F. J., Jahn, W. & Schröder, R. R. (2003) Nature 425, 423-427], supplemented with several heretofore missing residues, thus realizing the "strongly bound state." Comparing states suggests how influences initiated at the interface travel elsewhere in myosin to discharge various functions, including striking the actins. Overall, state change seems to occur by attachment of a hydrophobic triplet (Trp-546, Phe-547, and Pro-548) of myosin to an actin conduit with a hydrophobic guiding rail (Ile-341, Ile-345, Leu-349, and Phe-352) and the subsequent linear movement of the triplet along the rail.

A bond graph model of chemo-mechanical transduction in the mammalian left ventricle

We present a new lumped model of the pump behaviour of the mammalian left ventricle based on simple but physiologically plausible sub-models of chemo-mechanical energy transduction in muscle, mechano-hydraulic energy transduction in the ventricular wall and hemodynamical coupling of the ventricle and its arterial load. The model builds upon the foundation of classical analog ventricular models (dynamic compliance and visco-elastic models). However, we show that these classical models are not coherent from an energy viewpoint. To insure this coherency, we introduce explicit cross-bridge mechanisms linked to the mechano-hydraulical part of the model by a two-port capacitive (2PC) transducer representing chemo-mechanical coupling. We show that this 2PC is thermodynamically plausible and, when coupled to dissipative models of chemical energy generation and transfer, provides a novel and consistent characterisation of cardiac energetics at the global pump level. Finally, we briefly discuss some generalisations using nonlinear elements described by functional equations to represent muscle memory and sur-activation. It is a well-known fact that languages shape perception. Of all the lumped modelling languages, the bond graph (BG) method is the only one to use the notion of a 2PC as a primitive modelling concept. Our hypothesis (mental model) is thus directly inspired by the fact that we use the BG language. Our claim is thus that our work demonstrates very clearly the heuristic and descriptive power of BGs in shaping new ideas about multi-energy and nonlinear physiological applications.

The structure of myosin and its role in energy transduction in muscle.

The present understanding of the relationship between the structure of the myosin ATPase and its role in force production for muscle contraction is reviewed. Emphasis is placed on structural transitions in myosin that occur during ATP hydrolysis which may be correlated with force production. Although detailed structural information is presently lacking, numerous spectroscopic and kinetic experiments have indicated that myosin exists in two structural states for each chemical intermediate in the hydrolysis of ATP. Models are discussed which view a transition between these two states as the energy transduction "event" (i.e., force production).

Binding of [14C]DDT and [14C]dicyclohexylcarbodi‐imide to a lipoprotein of the membrane sector of mitochondrial ATpase

AbstractIntact mitochondria, isolated from red coxal muscle of the American cockroach (Periplaneta americana L.), were incubated in the presence of 1,1,1‐trichloro‐2,2‐bis(4‐chloro[14C]phenyl)ethane ([14C]DDT) to isolate a suspected binding site for DDT in the membrane sector of the mitochondrial ATPase. The requirements for the binding of DDT were compared with those for the binding of dicyclohexyl[14C]carbodi‐imide([14C]DCCD), a potent inhibitory probe of mitochondrial ATPase activity. [14C]DDT appeared to bind to a proteolipid of the membrane sector, which also binds [14C]DCCD. Exchange experiments, with [14C]DCCD, [14C]DDT and unlabelled DDT at different concentrations, indicated that DDT and DCCD may be acting on a similar protein. This protein may act as the energy transducing protonophore required for the synthesis and hydrolysis of ATP in coupled mitochondria. Inhibition of mitochondrial ATPase activity may be a consequence of DDT and DCCD binding to this proteolipid protonophore, resulting in the disruption of energy transduction in muscle and nerve.

Rotational Motions of Muscle Proteins Studied by Saturation-Transfer Electron Paramagnetic Resonance

The sensitivity of saturation-transfer electron paramagnetic resonance to rotational motion in the submillisecond range provides a means of studying rotational motions of the myofibrillar proteins of muscle and segments of these proteins. Estimates of these rotational motions have been made using purified proteins and supramolecular complexes that have been formed by assembly of purified proteins or isolated as such by partially disrupting the intact muscle cell. These motions are of particular relevance to an understanding of the molecular basis of energy transduction in muscle, where the force-generating step is generally believed to involve rotation of the myosin crossbridge about some point on the actin filament. By selectively introducing rigidly bound spin labels into specific muscle proteins and into specific regions of these proteins it has been possible to obtain insights into the molecular motions of myosin and actin, and into the nature of interaction between these proteins.

On the molecular basis for chemomechanical energy transduction in muscle.

Herein it is developed that energy transduction in muscle is an activity of myosin S-1 and its ligands, actin (A) and nucleotide (N). S-1 shares with other molecular particles (e.g., hemoglobin) the property that binding events at one of its sites, the N-site, influences binding events at a remote site, the A site (specifically, influences both the actin affinity and actin attachment angle at the A site). However, there is a crucial difference between S-1 and the better-known systems. Because the N site is enzymatic, it has a temporal sequence of occupants; this imposes a temporal sequence of actin attitudes--i.e., a sequence of mechanical events.

The twelfth Colworth Medal lecture. The adenosine triphosphatase reactions of myosin and actomyosin and their relation to energy transduction in muscle.

The twelfth Colworth Medal lecture. The adenosine triphosphatase reactions of myosin and actomyosin and their relation to energy transduction in muscle.

A theory of covalent bonding in muscle contraction

A theory is proposed which describes the contraction of striated muscle in terms of a cycle of three covalent reactions: (1) The ATP, Mg 2+ activation of actin to form a covalent actin-ADP acyl derivative. (2) The formation of an isopeptide bond between actin and myosin by a Ca 2+-activated acyl-transferase reaction. (3) The splitting of the isopeptide bond. This theory accounts for a number of observations which cannot be explained by the current assumption that energy transduction in muscle is the consequence of myosin-catalyzed ATP hydrolysis.