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Media type:
E-Article
Title:
Graded titin cleavage progressively reduces tension and uncovers the source of A-band stability in contracting muscle
Contributor:
Li, Yong;
Hessel, Anthony L;
Unger, Andreas;
Ing, David;
Recker, Jannik;
Koser, Franziska;
Freundt, Johanna K;
Linke, Wolfgang A
Published:
eLife Sciences Publications, Ltd, 2020
Published in:
eLife, 9 (2020)
Language:
English
DOI:
10.7554/elife.64107
ISSN:
2050-084X
Origination:
Footnote:
Description:
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.