An ionic–chemical–mechanical model for muscle contraction

Abstract

The dynamic process underlying muscle contraction is the parallel sliding of thin actin filaments along an immobile thick myosin fiber powered by oar-like movements of protruding myosin cross bridges (myosin heads). The free energy for functioning of the myosin nanomotor comes from the hydrolysis of ATP bound to the myosin heads. The unit step of translational movement is based on a mechanical-chemical cycle involving ATP binding to myosin, hydrolysis of the bound ATP with ultimate release of the hydrolysis products, stress-generating conformational changes in the myosin cross bridge, and relief of built-up stress in the myosin power stroke. The cycle is regulated by a transition between weak and strong actin-myosin binding affinities. The dissociation of the weakly bound complex by addition of salt indicates the electrostatic basis for the weak affinity, while structural studies demonstrate that electrostatic interactions among negatively charged amino acid residues of actin and positively charged residues of myosin are involved in the strong binding interface. We therefore conjecture that intermediate states of increasing actin-myosin engagement during the weak-to-strong binding transition also involve electrostatic interactions. Methods of polymer solution physics have shown that the thin actin filament can be regarded in some of its aspects as a net negatively charged polyelectrolyte. Here we employ polyelectrolyte theory to suggest how actin-myosin electrostatic interactions might be of significance in the intermediate stages of binding, ensuring an engaged power stroke of the myosin motor that transmits force to the actin filament, and preventing the motor from getting stuck in a metastable pre-power stroke state. We provide electrostatic force estimates that are in the pN range known to operate in the cycle.

Bioderived DNA Nanomachines for Potential Uses in Biosensing, Diagnostics, and Therapeutic Applications

“…A promising way to address these challenges is by first drawing inspiration and design from biological nanomotors and incorporating existing biological modalities into our designs and second, working with a biological material such as DNA, to create synthetic DNA structures, which does not require many of the same harmful organic chemistries. Biological nanomotors, such as actin/myosin, kinesin, and the adenosine triphosphate (ATP) Fo/F1 motor can function to deliver cargo, move in biological environments, and have the ability to discern specific targets. We can derive inspiration from their motion and how they interact with stimuli within their environment to design our synthetic structures.…”