NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans.
NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans.
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DOI：
10.1039/c8lc00103k
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发表时间：
2018-07-24
期刊：
影响因子：
6.1
通讯作者：
Vanapalli SA
中科院分区：
文献类型：
--
作者：
Rahman M;Hewitt JE;Van-Bussel F;Edwards H;Blawzdziewicz J;Szewczyk NJ;Driscoll M;Vanapalli SA
肌肉力量是人类生活质量的功能性量度。肌肉力量的下降表现在疾病以及不活动，衰老和太空旅行期间。在保守的肌肉生物学特性下，简单的遗传模型C。elegans是一个高通量平台，在其中鉴定引起肌肉力量损失的分子机制，并开发基于饮食、运动和药物的干预措施。在临床上，标准化的力量测量对于量化患者的变化是必不可少的;然而，在C. elegans模型，因为力的产生基于动物的行为和运动而波动。在这里，我们报告了一种基于微流体的强度测量系统，我们称之为“NemaFlex”，基于线虫爬过柱子森林时的柱子偏转。我们已经优化了微柱森林设计，并确定了强大的测量条件，产生一个独立于行为和步态的强度测量。使用肌肉收缩剂和突变体的验证研究证实，NemaFlex可以可靠地对C.优雅的此外，我们报告了一个比例因子来解释动物的大小，这与生物力学模型一致，并使突变体的比较强度研究成为可能。综上所述，我们的研究结果锚NemaFlex在遗传和药物筛选中的应用，用于定义神经肌肉功能的分子和细胞回路，以及用于解剖废用、衰老和疾病中的退行性过程。
Muscle strength is a functional measure of quality of life in humans. Declines in muscle strength are manifested in diseases as well as during inactivity, aging, and space travel. With conserved muscle biology, the simple genetic model C. elegans is a high throughput platform in which to identify molecular mechanisms causing muscle strength loss and to develop interventions based on diet, exercise, and drugs. In the clinic, standardized strength measures are essential to quantitate changes in patients; however, analogous standards have not been recapitulated in the C. elegans model since force generation fluctuates based on animal behavior and locomotion. Here, we report a microfluidics-based system for strength measurement that we call ‘NemaFlex’, based on pillar deflection as the nematode crawls through a forest of pillars. We have optimized the micropillar forest design and identified robust measurement conditions that yield a measure of strength that is independent of behavior and gait. Validation studies using a muscle contracting agent and mutants confirm that NemaFlex can reliably score muscular strength in C. elegans. Additionally, we report a scaling factor to account for animal size that is consistent with a biomechanics model and enables comparative strength studies of mutants. Taken together, our findings anchor NemaFlex for applications in genetic and drug screens, for defining molecular and cellular circuits of neuromuscular function, and for dissection of degenerative processes in disuse, aging, and disease.
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影响因子：
2.6
作者：
Lerario A;Bonfiglio S;Sormani M;Tettamanti A;Marktel S;Napolitano S;Previtali S;Scarlato M;Natali-Sora M;Mercuri E;Bresolin N;Mongini T;Comi G;Gatti R;Ciceri F;Cossu G;Torrente Y
通讯作者：
Torrente Y
影响因子：
6.1
作者：
Doll JC;Harjee N;Klejwa N;Kwon R;Coulthard SM;Petzold B;Goodman MB;Pruitt BL
通讯作者：
Pruitt BL
影响因子：
3.2
作者：
Khare, Siddharth M.;Awasthi, Anjali;Koushika, Sandhya P.
通讯作者：
Koushika, Sandhya P.
DOI：
10.1093/gerona/63.8.829
发表时间：
2008-08-01
影响因子：
5.1
作者：
Clark, Brian C.;Manini, Todd M.
通讯作者：
Manini, Todd M.
影响因子：
64.8
作者：
Herndon, LA;Schmeissner, PJ;Driscoll, M
通讯作者：
Driscoll, M