The distinctive mechanical and structural signatures of residual force enhancement in myofibers
In muscle, titin proteins connect myofilaments together and are thought to be critical for contraction, especially during residual force enhancement (RFE) when steady-state force is elevated after an active stretch. We investigated titin's function during contraction using small-angle X-ray diffraction to track structural changes before and after 50% titin cleavage and in the RFE-deficient, <i>mdm</i> titin mutant. We report that the RFE state is structurally distinct from pure isometric contractions, with increased thick filament strain and decreased lattice spacing, most likely caused by elevated titin-based forces. Furthermore, no RFE structural state was detected in <i>mdm</i> muscle. We posit that decreased lattice spacing, increased thick filament stiffness, and increased non-cross-bridge forces are the major contributors to RFE. We conclude that titin directly contributes to RFE.
Authors
- Thomas C. Irving (ORCID: https://orcid.org/0000-0003-4848-3323)
- Anthony L. Hessel (ORCID: https://orcid.org/0000-0003-4278-4221)
- Weikang Ma (ORCID: https://orcid.org/0000-0001-9535-7114)
- Kiisa C. Nishikawa (ORCID: https://orcid.org/0000-0001-8252-0285)
- Venus Joumaa (ORCID: https://orcid.org/0000-0001-7720-881X)
- Bradley M. Palmer (ORCID: https://orcid.org/0000-0002-4388-3160)
- Johanna K. Freundt (ORCID: https://orcid.org/0009-0009-1356-7624)
- Wolfgang A. Linke (ORCID: https://orcid.org/0000-0003-0801-3773)
- Devin Nissen (ORCID: https://orcid.org/0000-0001-9751-0901)
- Dhruv Mishra (ORCID: https://orcid.org/0000-0003-3652-6189)
- M. Kuehn (ORCID: https://orcid.org/0000-0001-7232-2517)
Institutions
- University of Vermont (US)
- University of Calgary (CA)
- Illinois Institute of Technology (US)
- Northern Arizona University (US)
- Universitätsmedizin Göttingen (DE)
- German Centre for Cardiovascular Research (DE)
- Czech Academy of Sciences, Institute of Physiology (CZ)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2024-12-16
- DOI
- https://doi.org/10.1073/pnas.2413883121
- Citations
- 12
- Primary Topic
- Cardiomyopathy and Myosin Studies
- Type
- article
- Field-Weighted Citation Impact
- 4.82
Funders
- National Science Foundation
- U.S. Department of Energy
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- Office of Science
- National Heart, Lung, and Blood Institute
- National Institute of General Medical Sciences
- Argonne National Laboratory