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Tension sensor based on fluorescence resonance energy transfer reveals fiber diameter-dependent mechanical factors during myelination
Frontiers in Cellular Neuroscience ( IF 4.2 ) Pub Date : 2021-07-13 , DOI: 10.3389/fncel.2021.685044
Takeshi Shimizu 1 , Hideji Murakoshi 2, 3 , Hidetoshi Matsumoto 4 , Kota Ichino 4 , Atsunori Hattori 1 , Shinya Ueno 1 , Akimasa Ishida 1 , Naoki Tajiri 1 , Hideki Hida 1
Affiliation  

Oligodendrocytes (OLs) form a myelin sheath around neuronal axons to increase conduction velocity of action potential. Although both large and small diameter axons are intermingled in the central nervous system, the number of myelin wrapping is related to the axon diameter, such that the ratio of the diameter of the axon to that of the entire myelinated-axon unit is optimal for each axon, which is required for exerting higher brain functions. This indicates there are unknown axon diameter-dependent factors that control myelination. We tried to investigate physical factors to clarify the mechanisms underlying axon diameter-dependent myelination. To visualize OL-generating forces during myelination, a tension sensor based on fluorescence resonance energy transfer (FRET) was used. Polystyrene nanofibers with varying diameters similar to neuronal axons were prepared to investigate biophysical factors regulating the OL-axon interactions. We found that higher tension was generated at OL processes contacting larger diameter fibers compared with smaller diameter fibers. Additionally, OLs formed longer focal adhesions (FAs) on larger diameter axons and shorter FAs on smaller diameter axons. These results suggest that OLs respond to the fiber diameter and activate mechanotransduction initiated at FAs, which controls their cytoskeletal organization and myelin formation. This study leads to the novel and interesting idea that physical factors are involved in myelin formation in response to axon diameter.

中文翻译:

基于荧光共振能量转移的张力传感器揭示髓鞘形成过程中与纤维直径相关的机械因素

少突胶质细胞 (OLs) 在神经元轴突周围形成髓鞘,以增加动作电位的传导速度。尽管中枢神经系统中大直径轴突和小直径轴突混合在一起,但髓鞘包裹的数量与轴突直径有关,因此轴突直径与整个有髓轴突单元的直径比对于每个轴突都是最佳的。轴突,这是发挥更高的大脑功能所必需的。这表明存在控制髓鞘形成的未知轴突直径依赖性因素。我们试图研究物理因素以阐明轴突直径依赖性髓鞘形成的机制。为了在髓鞘形成过程中可视化 OL 生成力,使用了基于荧光共振能量转移 (FRET) 的张力传感器。制备了直径与神经元轴突相似的不同直径的聚苯乙烯纳米纤维,以研究调节 OL-轴突相互作用的生物物理因素。我们发现,与直径较小的纤维相比,接触较大直径纤维的 OL 工艺会产生更高的张力。此外,OL 在较大直径的轴突上形成较长的粘着斑 (FA),在较小直径的轴突上形成较短的 FA。这些结果表明 OLs 响应纤维直径并激活在 FAs 处启动的机械转导,从而控制它们的细胞骨架组织和髓鞘形成。这项研究产生了一个新颖有趣的想法,即物理因素参与了髓鞘形成以响应轴突直径。我们发现,与直径较小的纤维相比,接触较大直径纤维的 OL 工艺会产生更高的张力。此外,OL 在较大直径的轴突上形成较长的粘着斑 (FA),在较小直径的轴突上形成较短的 FA。这些结果表明 OLs 响应纤维直径并激活在 FAs 处启动的机械转导,从而控制它们的细胞骨架组织和髓鞘形成。这项研究产生了一个新颖有趣的想法,即物理因素参与了髓鞘形成以响应轴突直径。我们发现,与直径较小的纤维相比,接触较大直径纤维的 OL 工艺会产生更高的张力。此外,OL 在较大直径的轴突上形成较长的粘着斑 (FA),在较小直径的轴突上形成较短的 FA。这些结果表明 OLs 响应纤维直径并激活在 FAs 处启动的机械转导,从而控制它们的细胞骨架组织和髓鞘形成。这项研究产生了一个新颖有趣的想法,即物理因素参与了髓鞘形成以响应轴突直径。这些结果表明 OL 对纤维直径有反应,并激活在 FA 处启动的机械转导,从而控制它们的细胞骨架组织和髓鞘形成。这项研究产生了一个新颖有趣的想法,即物理因素参与了髓鞘形成以响应轴突直径。这些结果表明 OLs 响应纤维直径并激活在 FAs 处启动的机械转导,从而控制它们的细胞骨架组织和髓鞘形成。这项研究产生了一个新颖有趣的想法,即物理因素参与了髓鞘形成以响应轴突直径。
更新日期:2021-07-14
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