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Microtubules provide a viscoelastic resistance to myocyte motion

Background Microtubules (MT) buckle and bear load during myocyte contraction, a behavior enhanced by post-translational detyrosination. This buckling suggests a spring-like resistance against myocyte shortening, which could store energy and aid myocyte relaxation. Despite this visual suggesting of elastic behavior, the precise mechanical contribution of the cardiac MT network remains to be defined. Methods Here we experimentally and computationally probe the mechanical contribution of stable microtubules and their influence on myocyte function. We use multiple approaches to interrogate viscoelasticity and cell shortening in primary murine myocytes where either MTs are depolymerized or detyrosination is suppressed, and use the results to inform a mathematical model of myocyte viscoelasticity. Results MT ablation by colchicine concurrently enhances both the degree of shortening and speed of relaxation, a finding inconsistent with simple spring-like microtubule behavior, and suggestive of a viscoelastic mechanism. Axial stretch and transverse indentation confirm that microtubules increase myocyte viscoelasticity. Specifically, increasing the rate of strain amplifies the MT contribution to myocyte stiffness. Suppressing MT detyrosination with parthenolide or via overexpression of tubulin tyrosine ligase (TTL) has mechanical consequences that closely resemble colchicine, suggesting that the mechanical impact of MTs relies on a detyrosination-dependent linkage with the myocyte cytoskeleton. Mathematical modeling affirms that alterations in cell shortening conferred by either MT destabilization or tyrosination can be attributed to internal changes in myocyte viscoelasticity. Conclusions The results suggest that the cardiac MT network regulates contractile amplitudes and kinetics by acting as a cytoskeletal shock-absorber, whereby MTs provide breakable cross-links between the sarcomeric and non-sarcomeric cytoskeleton that resist rapid length changes during both shortening and stretch.