biostudies-literatureUnknownHessel ALIn muscle, titin proteins connect myofilaments together and are thought to be critical for contraction, especially during residual force enhancement (RFE) when 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-crossbridge forcesbioRxiv : the preprint server for biology2023.02.19.529125https://www.ebi.ac.uk/biostudies/studies/S-EPMC9980001biostudies-literatureThe distinctive mechanical and structural signatures of residual force enhancement in myofibers.PMC9980001Mishra DNishikawa KCLinke WANissen DKuehn MPalmer BMHessel ALFreundt JIrving TJoumaa VMa WfalseThe 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 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-crossbridge forces2023-01-01T00:00:00Z2023 Feb2025-04-04T18:51:02.786Z2025-04-04T18:51:02.786ZS-EPMC99800013686526610.1101/2023.02.19.529125