The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice
The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice
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DOI：
10.1038/s41598-019-46723-6
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发表时间：
2019-07-24
影响因子：
4.6
通讯作者：
Friedrich, Oliver
中科院分区：
文献类型：
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作者：
Haug, Michael;Meyer, Charlotte;Friedrich, Oliver
编码肌肉特异性中间丝蛋白结蛋白的Des基因的突变导致肌病和心肌病。我们先前产生了R349 P结蛋白敲入小鼠品系作为相应的最常见的人结蛋白突变R350 P的患者模拟模型。由于对受影响肌肉的生物力学的年龄依赖性变化一无所知，我们研究了来自年轻（17-23周）、成年（25-45周）和老年（>60周）杂合和纯合R349 P结蛋白敲入小鼠的小纤维束与野生型同窝小鼠相比的被动和主动生物力学。我们使用了一种新的自动化生物机电平台，MyoRobot，进行连贯的定量记录被动（静息长度-张力曲线，粘弹性）和主动（咖啡因诱导的力瞬变，pCa力，松弛测试）参数，以确定年龄依赖性的影响，R349 P结蛋白突变慢收缩比目鱼肌和快收缩趾长伸肌小纤维束。我们证明，主动力的特性不受这种突变的影响，而被动的稳态弹性在R349 P结蛋白纤维束与表现出更硬的肌肉制剂的预老化表型兼容大大改变。另一方面，粘弹性没有改变。我们的研究代表了第一个系统的年龄相关的表征小肌肉纤维束制备生物力学与遗传性结蛋白病。
Mutations in the Des gene coding for the muscle-specific intermediate filament protein desmin lead to myopathies and cardiomyopathies. We previously generated a R349P desmin knock-in mouse strain as a patient-mimicking model for the corresponding most frequent human desmin mutation R350P. Since nothing is known about the age-dependent changes in the biomechanics of affected muscles, we investigated the passive and active biomechanics of small fiber bundles from young (17-23 wks), adult (25-45 wks) and aged (>60 wks) heterozygous and homozygous R349P desmin knock-in mice in comparison to wild-type littermates. We used a novel automated biomechatronics platform, the MyoRobot, to perform coherent quantitative recordings of passive (resting length-tension curves, visco-elasticity) and active (caffeine-induced force transients, pCa-force, 'slack-tests') parameters to determine age-dependent effects of the R349P desmin mutation in slow-twitch soleus and fast-twitch extensor digitorum longus small fiber bundles. We demonstrate that active force properties are not affected by this mutation while passive steady-state elasticity is vastly altered in R349P desmin fiber bundles compatible with a pre-aged phenotype exhibiting stiffer muscle preparations. Visco-elasticity on the other hand, was not altered. Our study represents the first systematic age-related characterization of small muscle fiber bundle preparation biomechanics in conjunction with inherited desminopathy.