Abstract
In muscle, but not in single-molecule mechanics studies, actin, myosin and accessory proteins are incorporated into a highly ordered myofilament lattice. In view of this difference we compare results from single-molecule studies and muscle mechanics and analyze to what degree data from the two types of studies agree with each other. There is reasonable correspondence in estimates of the cross-bridge power-stroke distance (7–13 nm), cross-bridge stiffness (~2 pN/nm) and average isometric force per cross-bridge (6–9 pN). Furthermore, models defined on the basis of single-molecule mechanics and solution biochemistry give good fits to experimental data from muscle. This suggests that the ordered myofilament lattice, accessory proteins and emergent effects of the sarcomere organization have only minor modulatory roles. However, such factors may be of greater importance under e.g., disease conditions. We also identify areas where single-molecule and muscle data are conflicting: (1) whether force generation is an Eyring or Kramers process with just one major power-stroke or several sub-strokes; (2) whether the myofilaments and the cross-bridges have Hookean or non-linear elasticity; (3) if individual myosin heads slip between actin sites under certain conditions, e.g., in lengthening; or (4) if the two heads of myosin cooperate.
Highlights
Contraction of striated muscle is the result of adenosine triphosphate (ATP)-driven cyclic interactions between the contractile proteins myosin II and actin (Figure 1)
Another complication for muscle experiments is that the actual number of attached cross-bridges that contribute to stiffness in muscle fibers in rigor is not known with 100% certainty [203,204,205] despite evidence suggesting that all myosin heads bind to actin in rigor [206]
Despite the differences and various complications associated with both single-molecule studies and muscle mechanics the two types of studies give surprisingly consistent information about cross-bridge function
Summary
Contraction of striated muscle is the result of adenosine triphosphate (ATP)-driven cyclic interactions between the contractile proteins myosin II (often “myosin” below) and actin (Figure 1). TThheesseelfl-fa-asssseemmbblylyooff mmuultltipiprrooteteinin ffiillaammeennttss iinnttoo tthhee hhiigghhllyy oorrddeerreedd mmyyooffiillaammeenntt llaattttiiccee [[1111]] iiss eesssseennttiiaall ffoorr tthhee eeffffeeccttiivvee ooppeerraattiioonn ooff tthhee hhaallff--ssaarrccoommeerree bbuutt tthhiiss oorrddeerreedd aarrrraannggeemmeenntt iiss nneecceessssaarriillyy lloosstt iinn ssiinnggllee--mmoolleeccuullee mmeecchhaanniiccssssttuuddiieess..OOnntthheenneexxtthhiieerraarrcchhiiccaalllleevveell,, tthhee hhaallff--ssaarrccoommeerreess aarree sseerriiaallllyy iinntteerrccoonnnneecctteedd ttooffoorrmmaammyyooffiibbrriillooff11––22μμmmddiaiammeetteerr..FFuurrtthheerrmmoorree,, tthheemmyyooffiibbrriillssaarreeaarrrraannggeeddiinnppaarraalllleellwwiitthhtthheessaarrccoommeerreeppaatttteerrnnllaarrggeellyy iinnrreeggiisstteerroovveerrtthheemmuussccllee ffiibbeerr ccrroossss--sseeccttiioonn dduuee ttoo iinntteerrccoonnnneeccttiioonnss vviiaa iinntteerrmmeeddiiaarryy ffiillaammeennttss ssuucchh aass ddeessmmiinn bbeettwweeeenn ssaarrccoommeerree ZZ--lliinneess ooff nneeiigghhbboorriinngg mmyyooffiibbrriillss. An early example was the demonstration of ~10 nm steps of myosin along actin seen in the optical tweezers studies of Finer et al [57] This finding corroborated ideas for the main force-, and motion-generating conformational change in myosin inferred from X-ray crystallography just a year earlier [74,75]. More detailed quantitative information can be obtained as considered in detail below
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