| First Author | Li Y | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 33357376 | Mgi Jnum | J:341762 |
| Mgi Id | MGI:6705888 | Doi | 10.7554/eLife.64107 |
| Citation | Li Y, et al. (2020) Graded titin cleavage progressively reduces tension and uncovers the source of A-band stability in contracting muscle. Elife 9 |
| abstractText | The giant muscle protein titin is a major contributor to passive force; however, its role in active force generation is unresolved. Here, we use a novel titin-cleavage (TC) mouse model that allows specific and rapid cutting of elastic titin to quantify how titin-based forces define myocyte ultrastructure and mechanics. We show that under mechanical strain, as TC doubles from heterozygous to homozygous TC muscles, Z-disks become increasingly out of register while passive and active forces are reduced. Interactions of elastic titin with sarcomeric actin filaments are revealed. Strikingly, when titin-cleaved muscles contract, myosin-containing A-bands become split and adjacent myosin filaments move in opposite directions while also shedding myosins. This establishes intact titin filaments as critical force-transmission networks, buffering the forces observed by myosin filaments during contraction. To perform this function, elastic titin must change stiffness or extensible length, unveiling its fundamental role as an activation-dependent spring in contracting muscle. |
