{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T23:43:47Z","timestamp":1786319027933,"version":"build-2736575974"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Crossbridge binding, state transitions, and force in active muscle is dependent on the radial spacing between the myosin-containing thick filament and the actin-containing thin filament in the filament lattice. This radial spacing has been previously shown through spatially explicit modeling and experimental efforts to greatly affect quasi-static, isometric, force production in muscle. It has recently been suggested that this radial spacing might also be able to drive differences in mechanical function, or net work, under dynamic oscillations like those which occur in muscles <jats:italic>in vivo<\/jats:italic>. However, previous spatially explicit models either had no radial spacing dependence, meaning the radial spacing could not be investigated, or did include radial spacing dependence but could not reproduce <jats:italic>in vivo<\/jats:italic> net work during dynamic oscillations and only investigated isometric contractions. Here we show the first spatially explicit model to include radial crossbridge dependence which can produce mechanical function similar to real muscle. Using this spatially explicit model of a half sarcomere, we show that when oscillated at strain amplitudes and frequencies like those in the main flight muscles of the hawkmoth <jats:italic>Manduca sexta<\/jats:italic>, mechanical function (net work) does depend on the lattice spacing. In addition, since the trajectory of lattice spacing changes during dynamic oscillation can vary from organism to organism, we can prescribe a trajectory of lattice spacing changes in the spatially explicit half sarcomere model and investigate the extent to which the time course of lattice spacing changes can affect mechanical function. We simulated a half sarcomere undergoing dynamic oscillations and prescribed the Poisson\u2019s ratio of the lattice to be either 0 (constant lattice spacing) or 0.5 (isovolumetric lattice spacing changes). We also simulated net work using lattice spacing data taken from <jats:italic>M. sexta<\/jats:italic> which has a variable Poisson\u2019s ratio. Our simulation results indicate that the lattice spacing can change the mechanical function of muscle, and that in some cases a 1 nm difference can switch the net work of the half sarcomere model from positive (motor-like) to negative (brake-like).<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012862","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T17:43:49Z","timestamp":1744911829000},"page":"e1012862","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nanometer scale difference in myofilament lattice structure of muscle alters muscle function in a spatially explicit model"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1320-1904","authenticated-orcid":true,"given":"Travis 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Wang","year":"1995","journal-title":"J Mol Cell Cardiol"},{"issue":"2","key":"pcbi.1012862.ref023","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1152\/physrev.2000.80.2.853","article-title":"Regulation of contraction in striated muscle","volume":"80","author":"AM Gordon","year":"2000","journal-title":"Physiol Rev"},{"issue":"4","key":"pcbi.1012862.ref024","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/S0006-3495(98)77875-0","article-title":"Compliant realignment of binding sites in muscle: transient behavior and mechanical tuning","volume":"74","author":"TL Daniel","year":"1998","journal-title":"Biophys J"},{"issue":"7","key":"pcbi.1012862.ref025","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1371\/journal.pcbi.0030115","article-title":"Sarcomere lattice geometry influences cooperative myosin binding in muscle","volume":"3","author":"BCW Tanner","year":"2007","journal-title":"PLoS Comput 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Lymn","year":"1971","journal-title":"Biochemistry"},{"issue":"2","key":"pcbi.1012862.ref039","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0022-5193(86)80135-7","article-title":"A model for the interaction of muscle cross-bridges with ligands which compete with ATP","volume":"118","author":"E Pate","year":"1986","journal-title":"J Theor Biol"},{"issue":"5321","key":"pcbi.1012862.ref040","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/233533a0","article-title":"Proposed mechanism of force generation in striated muscle","volume":"233","author":"AF Huxley","year":"1971","journal-title":"Nature"},{"issue":"4","key":"pcbi.1012862.ref041","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.jmb.2006.07.084","article-title":"Electron tomography of swollen rigor fibers of insect flight muscle reveals a short and variably angled S2 domain","volume":"362","author":"J Liu","year":"2006","journal-title":"J Mol 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Physiol"},{"key":"pcbi.1012862.ref048"},{"key":"pcbi.1012862.ref049"},{"issue":"6553","key":"pcbi.1012862.ref050","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/378209a0","article-title":"Movement and force produced by a single myosin head","volume":"378","author":"JE Molloy","year":"1995","journal-title":"Nature"},{"issue":"1744","key":"pcbi.1012862.ref051","first-page":"3958","article-title":"Abdicating power for control: a precision timing strategy to modulate function of flight power muscles","volume":"279","author":"S Sponberg","year":"2012","journal-title":"Proc Biol Sci"},{"key":"pcbi.1012862.ref052"},{"key":"pcbi.1012862.ref053"},{"issue":"14","key":"pcbi.1012862.ref054","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":"WA Linke","year":"1998","journal-title":"Proc Natl Acad Sci U S 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