The distinctive mechanical and structural signatures of residual force enhancement in myofibers

• 成果类型: Article
• 署名作者: Hessel, Anthony L.; Kuehn, Michel N.; Palmer, Bradley M.; Nissen, Devin; Mishra, Dhruv; Joumaa, Venus; Freundt, Johanna K.; Ma, Weikang; Nishikawa, Kiisa C.; Irving, Thomas C.; Linke, Wolfgang A.
• 署名单位: University of Munster; University of Vermont; Illinois Institute of Technology; Northern Arizona University; University of Calgary; University of Gottingen; UNIVERSITY GOTTINGEN HOSPITAL; German Centre for Cardiovascular Research
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12507
• DOI: 10.1073/pnas.2413883121
• 发表日期: 2024-12-24
• 关键词: length-dependent activation; myosin-filaments; actin-filaments; muscle-fibers; titin; thick; extensibility; myofibrils; tension; binding

摘要

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, mdm 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 mdm 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.