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While recent evidence suggests that microtubules enriched in detyrosinated \u03b1-tubulin regulate these processes in healthy muscle and increase them in disease, the possible contribution from several other \u03b1-tubulin modifications has not been investigated. Here, we used genetic and pharmacologic strategies in isolated cardiomyocytes and skeletal myofibers to increase the level of acetylated \u03b1-tubulin without altering the level of detyrosinated \u03b1-tubulin. We show that microtubules enriched in acetylated \u03b1-tubulin increase cytoskeletal stiffness and viscoelastic resistance. These changes slow rates of contraction and relaxation during unloaded contraction and increased activation of NADPH oxidase 2 (Nox2) by mechanotransduction. Together, these findings add to growing evidence that microtubules contribute to the mechanobiology of striated muscle in health and disease.<\/jats:p>","DOI":"10.1085\/jgp.202012743","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T02:20:56Z","timestamp":1614651656000},"update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":67,"title":["Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle"],"prefix":"10.1085","volume":"153","author":[{"given":"Andrew K.","family":"Coleman","sequence":"first","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7658-504X","authenticated-orcid":true,"given":"Humberto C.","family":"Joca","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoli","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8488-2180","authenticated-orcid":true,"given":"W. 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