{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T06:51:36Z","timestamp":1781592696375,"version":"3.54.5"},"reference-count":66,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["NSF IOS 2016049"],"award-info":[{"award-number":["NSF IOS 2016049"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["NSF DBI 2021832"],"award-info":[{"award-number":["NSF DBI 2021832"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Muscular dystrophy with myositis (mdm) is a naturally occurring mutation in the mouse Ttn gene that results in higher passive stress in muscle fibers and intact muscles compared to wild-type (WT). The goal of this study was to test whether alternative splicing of titin exons occurs in mdm muscles, which contain a small deletion in the N2A-PEVK regions of titin, and to test whether splicing changes are associated with an increase in titin-based passive tension. Although higher levels of collagen have been reported previously in mdm muscles, here we demonstrate alternative splicing of titin in mdm skeletal muscle fibers. We identified Z-band, PEVK, and C-terminus Mex5 exons as splicing hotspots in mdm titin using RNA sequencing data and further reported upregulation in ECM-associated genes. We also treated skinned mdm soleus fiber bundles with trypsin, trypsin + KCl, and trypsin + KCL + KI to degrade titin. The results showed that passive stress dropped significantly more after trypsin treatment in mdm fibers (11 \u00b1 1.6 mN\/mm2) than in WT fibers (4.8 \u00b1 1 mN\/mm2; p = 0.0004). The finding that treatment with trypsin reduces titin-based passive tension more in mdm than in WT fibers supports the hypothesis that exon splicing leads to the expression of a stiffer and shorter titin isoform in mdm fibers. After titin extraction by trypsin + KCl + KI, mdm fibers (6.7 \u00b1 1.27 mN\/mm2) had significantly higher collagen-based passive stress remaining than WT fibers (2.6 \u00b1 1.3 mN\/mm2; p = 0.0014). We conclude that both titin and collagen contribute to higher passive tension of mdm muscles.<\/jats:p>","DOI":"10.3390\/ijms23168858","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T02:42:53Z","timestamp":1660099373000},"page":"8858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Contributions of Titin and Collagen to Passive Stress in Muscles from mdm Mice with a Small Deletion in Titin\u2019s Molecular Spring"],"prefix":"10.3390","volume":"23","author":[{"given":"Pabodha","family":"Hettige","sequence":"first","affiliation":[{"name":"Chemistry Department, University of Massachusetts Lowell, Lowell, MA 01854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruv","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011-5640, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9516-407X","authenticated-orcid":false,"given":"Henk","family":"Granzier","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8252-0285","authenticated-orcid":false,"given":"Kiisa","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011-5640, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2304-6960","authenticated-orcid":false,"given":"Matthew J.","family":"Gage","sequence":"additional","affiliation":[{"name":"Chemistry Department, University of Massachusetts Lowell, Lowell, MA 01854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.3233\/JND-160158","article-title":"Increasing Role of Titin Mutations in Neuromuscular Disorders","volume":"3","author":"Savarese","year":"2016","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/oxfordjournals.jbchem.a131291","article-title":"Connectin, an elastic protein from myofibrils","volume":"80","author":"Maruyama","year":"1976","journal-title":"J. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1073\/pnas.76.8.3698","article-title":"Titin: Major myofibrillar components of striated muscle","volume":"76","author":"Wang","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/345273a0","article-title":"A regular pattern of two types of 100-residue motif in the sequence of titin","volume":"345","author":"Labeit","year":"1990","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"753675","DOI":"10.1155\/2010\/753675","article-title":"Titin diversity\u2014Alternative splicing gone wild","volume":"2010","author":"Guo","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1161\/hh2301.100981","article-title":"The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system","volume":"89","author":"Bang","year":"2001","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0014-5793(96)00338-9","article-title":"A molecular map of titin\/connectin elasticity reveals two different mechanisms acting in series","volume":"385","author":"Gautel","year":"1996","journal-title":"Febs Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8052","DOI":"10.1073\/pnas.95.14.8052","article-title":"Nature of PEVK-titin elasticity in skeletal muscle","volume":"95","author":"Linke","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"C266","DOI":"10.1152\/ajpcell.1997.273.1.C266","article-title":"Basis of passive tension and stiffness in isolated rabbit myofibrils","volume":"273","author":"Bartoo","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e40532","DOI":"10.7554\/eLife.40532","article-title":"Downsizing the molecular spring of the giant protein titin reveals that skeletal muscle titin determines passive stiffness and drives longitudinal hypertrophy","volume":"7","author":"Brynnel","year":"2018","journal-title":"Elife"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1161\/01.RES.0000117769.88862.F8","article-title":"The giant protein titin: A major player in myocardial mechanics, signaling, and disease","volume":"94","author":"Granzier","year":"2004","journal-title":"Circ. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/S0006-3495(93)81482-6","article-title":"Viscoelasticity of the sarcomere matrix of skeletal muscles. The titin-myosin composite filament is a dual-stage molecular spring","volume":"64","author":"Wang","year":"1993","journal-title":"Biophys. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1161\/01.RES.86.11.1114","article-title":"Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity","volume":"86","author":"Freiburg","year":"2000","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1006\/jmbi.1996.0441","article-title":"Towards a molecular understanding of the elasticity of titin","volume":"261","author":"Linke","year":"1996","journal-title":"J. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1085\/jgp.200509364","article-title":"Isoform diversity of giant proteins in relation to passive and active contractile properties of rabbit skeletal muscles","volume":"126","author":"Prado","year":"2005","journal-title":"J. Gen. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1023\/A:1026053530766","article-title":"Gigantic variety: Expression patterns of titin isoforms in striated muscles and consequences for myofibrillar passive stiffness","volume":"24","author":"Neagoe","year":"2003","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1085\/jgp.201311129","article-title":"Removal of immunoglobulin-like domains from titin\u2019s spring segment alters titin splicing in mouse skeletal muscle and causes myopathy","volume":"143","author":"Buck","year":"2014","journal-title":"J. Gen. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1006\/geno.2002.6685","article-title":"The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin","volume":"79","author":"Garvey","year":"2002","journal-title":"Genomics"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nishikawa, K., Lindstedt, S.L., Hessel, A., and Mishra, D. (2020). N2A Titin: Signaling Hub and Mechanical Switch in Skeletal Muscle. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113974"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"C1092","DOI":"10.1152\/ajpcell.16.2008","article-title":"Early mechanical dysfunction of the diaphragm in the muscular dystrophy with myositis (Ttnmdm) model","volume":"295","author":"Lopez","year":"2008","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_21","first-page":"3110","article-title":"Titin force enhancement following active stretch of skinned skeletal muscle fibres","volume":"220","author":"Powers","year":"2017","journal-title":"J. Exp. Biol."},{"key":"ref_22","first-page":"1311","article-title":"Decreased force enhancement in skeletal muscle sarcomeres with a deletion in titin","volume":"219","author":"Powers","year":"2016","journal-title":"J. Exp. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"jeb200840","DOI":"10.1242\/jeb.200840","article-title":"Optimal length, calcium sensitivity and twitch characteristics of skeletal muscles from mdm mice with a deletion in N2A titin","volume":"222","author":"Hessel","year":"2019","journal-title":"J. Exp. Biol."},{"key":"ref_24","first-page":"4177","article-title":"Effects of a titin mutation on negative work during stretch-shortening cycles in skeletal muscles","volume":"220","author":"Hessel","year":"2017","journal-title":"J. Exp. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"jeb197038","DOI":"10.1242\/jeb.197038","article-title":"Effects of a titin mutation on force enhancement and force depression in mouse soleus muscles","volume":"223","author":"Tahir","year":"2020","journal-title":"J. Exp. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1093\/hmg\/ddi313","article-title":"Mdm muscular dystrophy: Interactions with calpain 3 and a novel functional role for titin\u2019s N2A domain","volume":"14","author":"Huebsch","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00359-016-1137-5","article-title":"The effects of a skeletal muscle titin mutation on walking in mice","volume":"203","author":"Pace","year":"2017","journal-title":"J. Comp. Physiol. A Neuroethol. Sens. Neural. Behav. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1242\/jeb.111849","article-title":"Shiver me titin! Elucidating titin\u2019s role in shivering thermogenesis","volume":"218","author":"Monroy","year":"2015","journal-title":"J. Exp. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"jeb198564","DOI":"10.1242\/jeb.198564","article-title":"Severe thermoregulatory deficiencies in mice with a deletion in the titin gene TTN","volume":"222","author":"Miyano","year":"2019","journal-title":"J. Exp. Biol."},{"key":"ref_30","first-page":"828","article-title":"Effects of activation on the elastic properties of intact soleus muscles with a deletion in titin","volume":"220","author":"Monroy","year":"2017","journal-title":"J. Exp. Biol."},{"key":"ref_31","first-page":"3629","article-title":"Titin force is enhanced in actively stretched skeletal muscle","volume":"217","author":"Powers","year":"2014","journal-title":"J. Exp. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1006\/jmcc.2000.1281","article-title":"Changes in titin and collagen underlie diastolic stiffness diversity of cardiac muscle","volume":"32","author":"Wu","year":"2000","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1126\/science.270.5234.293","article-title":"Titins: Giant proteins in charge of muscle ultrastructure and elasticity","volume":"270","author":"Labeit","year":"1995","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s10974-009-9189-6","article-title":"The vertebrate muscle Z-disc: Sarcomere anchor for structure and signalling","volume":"30","author":"Luther","year":"2009","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1093\/hmg\/10.13.1335","article-title":"Differential expression of the actin-binding proteins, alpha-actinin-2 and-3, in different species: Implications for the evolution of functional redundancy","volume":"10","author":"Mills","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/1097-0169(200103)48:3<190::AID-CM1008>3.0.CO;2-C","article-title":"Dynamics of alpha-actinin in focal adhesions and stress fibers visualized with alpha-actinin-green fluorescent protein","volume":"48","author":"Edlund","year":"2001","journal-title":"Cell Motil. Cytoskelet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1083\/jcb.110.6.1999","article-title":"Molecular genetics of Drosophila alpha-actinin: Mutant alleles disrupt Z disc integrity and muscle insertions","volume":"110","author":"Fyrberg","year":"1990","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/cm.20007","article-title":"Alpha-actinin revisited: A fresh look at an old player","volume":"58","author":"Otey","year":"2004","journal-title":"Cell Motil. Cytoskelet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1083\/jcb.114.3.481","article-title":"Disruption of the actin cytoskeleton after microinjection of proteolytic fragments of alpha-actinin","volume":"114","author":"Pavalko","year":"1991","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1083\/jcb.140.6.1383","article-title":"Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion","volume":"140","author":"Honda","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_41","first-page":"62","article-title":"Cloning and chromosomal localization of the human cytoskeletal alpha-actinin gene reveals linkage to the beta-spectrin gene","volume":"47","author":"Youssoufian","year":"1990","journal-title":"Am. J. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1242\/jcs.113.18.3329","article-title":"Actinin-4 is preferentially involved in circular ruffling and macropinocytosis in mouse macrophages: Analysis by fluorescence ratio imaging","volume":"113","author":"Araki","year":"2000","journal-title":"J. Cell Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/sj.onc.1203310","article-title":"The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells","volume":"19","author":"Nikolopoulos","year":"2000","journal-title":"Oncogene"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hettige, P., Tahir, U., Nishikawa, K.C., and Gage, M.J. (2020). Comparative analysis of the transcriptomes of EDL, psoas, and soleus muscles from mice. BMC Genom., 21.","DOI":"10.1186\/s12864-020-07225-2"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1529\/biophysj.104.057737","article-title":"Hierarchical extensibility in the PEVK domain of skeletal-muscle titin","volume":"89","author":"Nagy","year":"2005","journal-title":"Biophys. J."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hettige, P., Tahir, U., Nishikawa, K., and Gage, M. (BMC Genom., 2022). Transcriptomic profile of muscular dystrophy with myositis in extensor digitorum longus, psoas, and soleus muscles from mice, BMC Genom., in revision.","DOI":"10.1186\/s12864-022-08873-2"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1006\/jmbi.1997.1145","article-title":"Tissue-specific expression and alpha-actinin binding properties of the Z-disc titin: Implications for the nature of vertebrate Z-discs","volume":"270","author":"Sorimachi","year":"1997","journal-title":"J. Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1021\/bi002739r","article-title":"A structural characterization of the interactions between titin Z-repeats and the alpha-actinin C-terminal domain","volume":"40","author":"Joseph","year":"2001","journal-title":"Biochemistry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1073\/pnas.1612681114","article-title":"\u03b1-Actinin\/titin interaction: A dynamic and mechanically stable cluster of bonds in the muscle Z-disk","volume":"114","author":"Grison","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/S0022-2836(02)00372-8","article-title":"Muscle Z-band ultrastructure: Titin Z-repeats and Z-band periodicities do not match","volume":"319","author":"Luther","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.yjmcc.2009.01.004","article-title":"Titin-based mechanical signalling in normal and failing myocardium","volume":"46","author":"Kruger","year":"2009","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5781","DOI":"10.1242\/jcs.01501","article-title":"Differential actin binding along the PEVK domain of skeletal muscle titin","volume":"117","author":"Nagy","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.autrev.2010.12.009","article-title":"Alpha-actinin: A multidisciplinary protein with important role in B-cell driven autoimmunity","volume":"10","author":"Oikonomou","year":"2011","journal-title":"Autoimmun. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1093\/hmg\/ddr196","article-title":"Deficiency of alpha-actinin-3 is associated with increased susceptibility to contraction-induced damage and skeletal muscle remodeling","volume":"20","author":"Seto","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"9986","DOI":"10.1002\/jcb.27328","article-title":"Z-band and M-band titin splicing and regulation by RNA binding motif 20 in striated muscles","volume":"119","author":"Chen","year":"2018","journal-title":"J. Cell Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1006\/jmbi.1996.0108","article-title":"Genomic organization of M line titin and its tissue-specific expression in two distinct isoforms","volume":"256","author":"Kolmerer","year":"1996","journal-title":"J. Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"W3","DOI":"10.1093\/nar\/gkw343","article-title":"The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update","volume":"44","author":"Afgan","year":"2016","journal-title":"Nucleic. Acids. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"13716","DOI":"10.1073\/pnas.2235652100","article-title":"Calcium-dependent molecular spring elements in the giant protein titin","volume":"100","author":"Labeit","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"jeb243732","DOI":"10.1242\/jeb.243732","article-title":"Residual force enhancement is reduced in permeabilized fiber bundles from mdm muscles","volume":"225","author":"Mishra","year":"2022","journal-title":"J. Exp. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s004410050554","article-title":"Overshooting production of satellite cells in murine skeletal muscle affected by the mutation \u2033muscular dystrophy with myositis\u2033 (mdm, Chr 2)","volume":"283","author":"Heimann","year":"1996","journal-title":"Cell Tissue Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","article-title":"TopHat2: Accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions","volume":"14","author":"Kim","year":"2013","journal-title":"Genome. Biol."},{"key":"ref_63","first-page":"11","article-title":"Alternative Splicing Signatures in RNA-seq Data: Percent Spliced in (PSI)","volume":"87","author":"Schafer","year":"2015","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"ref_64","first-page":"e50183","article-title":"Evaluation of muscle function of the extensor digitorum longus muscle ex vivo and tibialis anterior muscle in situ in mice","volume":"72","author":"Hakim","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"C395","DOI":"10.1152\/ajpcell.00052.2014","article-title":"Calcium sensitivity of residual force enhancement in rabbit skinned fibers","volume":"307","author":"Joumaa","year":"2014","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s00424-007-0287-2","article-title":"Passive force enhancement in single myofibrils","volume":"455","author":"Joumaa","year":"2007","journal-title":"Pflug. Arch."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/8858\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:06:18Z","timestamp":1760141178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/8858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,9]]},"references-count":66,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23168858"],"URL":"https:\/\/doi.org\/10.3390\/ijms23168858","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,9]]}}}