{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:00:01Z","timestamp":1789682401903,"version":"4.0.1"},"reference-count":75,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"\n Abstract<\/jats:title>\n \n Regulation of myosin motor extension and conformation is central to cardiac muscle contraction\u2013relaxation, with myosin playing a critical role in mechanosensing during the cardiac cycle. Direct assessment of\n in vivo<\/jats:italic>\n dynamic interplay between myosin head position, cross\u2010bridge cycling, sarcomere shortening (filament sliding), muscle stress\u2013strain rates and pressure\u2013volume (PV) relationships is key to understanding both normal cardiac function and ventricle pathological states. This work aims to demonstrate that\n in vivo<\/jats:italic>\n temporal regulation of myosin head transfer to actin filaments in systole and diastole has important points of difference from current models based on\n in vitro<\/jats:italic>\n and\n ex vivo<\/jats:italic>\n muscle studies, particularly in settings of diastolic dysfunction. The first study investigated myosin activation\u2013deactivation in a mouse model of diet\u2010induced obesity (high\u2010fat high\u2010sugar diet) with moderate contraction\u2013relaxation impairment. In a second study myosin regulation was investigated in a novel hypertrophic cardiomyopathy mouse model due to a truncation mutation in the sarcomeric gene encoding cardiac myosin binging protein\u2010C,\n Mybpc3<\/jats:italic>\n (Exon 33 deletion). We demonstrate with\n in vivo<\/jats:italic>\n small\u2010angle X\u2010ray scattering (SAXS) simultaneous with PV loop analysis in the beating heart that dynamic regulation of myosin is often non\u2010uniform across the left ventricle from the epicardium to subendocardium, with large differences in myosin head behaviour in both systole and diastole, at least in rodents. Our findings underscore that myosin activation\u2013deactivation is intricately tuned to the mechanical demands of the heart and the work of each myocardial layer. Regional myosin filament dysregulation underpins muscle relaxation impairment, offering new insights into potential therapeutic targets.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n This small\u2010angle X\u2010ray scattering (SAXS) study demonstrates that\n in vivo<\/jats:italic>\n myosin activation\u2013deactivation and myosin interfilament spacing vary across myocardial layers and are influenced by diet, exercise and pathological conditions\n in vivo<\/jats:italic>\n in the murine heart.\n <\/jats:p>\n <\/jats:list-item>\n \n During the isovolumetric contraction phase, myosin heads exhibit strong cross\u2010bridge binding in response to mechanical load, which increases in the ejection phase, highlighting the critical role of mechanosensing in early force development. In the absence of myosin binding protein\u2010C within the thick filament complex this strong cross\u2010bridge formation is not sustained during ejection.<\/jats:p>\n <\/jats:list-item>\n \n Impaired myosin cross\u2010bridge detachment likely contributes to sustained cross\u2010bridge activation in the isovolumetric relaxation phase and prolongation of relaxation in hypertrophic cardiomyopathy.<\/jats:p>\n <\/jats:list-item>\n \n This study highlights how disturbed myosin mechanosensing evoked by metabolic stress and genetic mutations can impair myosin motor function and correlates with global cardiac dysfunction.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp287759","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T04:38:46Z","timestamp":1762835926000},"page":"6895-6924","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Myosin motor dynamics and cardiac function: Insights from\n in vivo<\/i>\n small\u2010angle X\u2010ray scattering and pressure\u2013volume analysis"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3318-5406","authenticated-orcid":false,"given":"James T.","family":"Pearson","sequence":"first","affiliation":[{"name":"Department of Cardiac Physiology National Cerebral and Cardiovascular Center Research Institute Suita\u2010shi Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-9455","authenticated-orcid":false,"given":"Mark T.","family":"Waddingham","sequence":"additional","affiliation":[{"name":"Department of Cardiac Physiology National Cerebral and Cardiovascular Center Research Institute Suita\u2010shi Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7591-2520","authenticated-orcid":false,"given":"Hirotsugu","family":"Tsuchimochi","sequence":"additional","affiliation":[{"name":"Department of Cardiac Physiology National Cerebral and Cardiovascular Center Research Institute Suita\u2010shi Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Sonobe","sequence":"additional","affiliation":[{"name":"Department of Bioregulatory Science Nippon Medical School Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Tokuhara","sequence":"additional","affiliation":[{"name":"Department of Cardiac Physiology National Cerebral and Cardiovascular Center Research Institute Suita\u2010shi Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Cardiac Physiology National Cerebral and Cardiovascular Center Research Institute Suita\u2010shi Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Junayed","family":"Nayeem","sequence":"additional","affiliation":[{"name":"Department of Cardiac Physiology National Cerebral and Cardiovascular Center Research Institute Suita\u2010shi Osaka Japan"},{"name":"Department of Biological Sciences Asian University for Women Chattogram Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-3507","authenticated-orcid":false,"given":"Yoshitaka","family":"Fujihara","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical Technologies National Cerebral and Cardiovascular Center Research Institute Suita\u2010shi Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohki","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Japan Synchrotron Radiation Research Institute\/JASRI Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2742-5426","authenticated-orcid":false,"given":"Christoph","family":"Maack","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center Department of Translational Science University Clinic W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9192-7674","authenticated-orcid":false,"given":"Vasco","family":"Sequeira","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center Department of Translational Science University Clinic W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-008-0501-x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1809540115"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00913.2013"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-042222-022728"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2007.10.088"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00929.2012"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1532-429X-12-48"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.12.063"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.178996"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.183897"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00586-4"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.111.965772"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06691-4"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.561472"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.123.011435"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.03.009"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908736116"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00581.2025"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780199570164.003.0009"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.323988"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2006.06.026"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-024-01063-5"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.5.H2568"},{"issue":"2","key":"e_1_2_6_25_1","article-title":"The structural OFF and ON states of myosin can be decoupled from the biochemical super\u2010 and disordered\u2010relaxed states","volume":"3","author":"Jani V. 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