The cytoskeleton is essential for spatial and temporal organisation of a wide range of cellular and tissue-level processes, such as proliferation, signalling, cargo transport, migration, morphogenesis, and neuronal development. Cytoskeleton research aims to study these processes by imaging, or by locally manipulating, the dynamics and organisation of cytoskeletal proteins with high spatiotemporal resolution: which matches the capabilities of optical methods. To date, no photoresponsive microtubule-stabilising tool has united all the features needed for a practical high-precision reagent: a low potency and biochemically stable non-illuminated state; then an efficient, rapid, and clean photoresponse that generates a high potency illuminated state; plus good solubility at suitable working concentrations; and efficient synthetic access. We now present CouEpo, a photocaged epothilone microtubule-stabilising reagent that combines these needs. Its potency increases approximately 100-fold upon violet/blue irradiation to reach low-nanomolar values, allowing efficient photocontrol of microtubule dynamics in live cells, and even the generation of cellular asymmetries in microtubule architecture and cell dynamics. CouEpo is thus a high-performance tool compound that can support high-precision research into many microtubule-associated processes, from biophysics to transport, cell motility, and neuronal physiology.

中文翻译：

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光笼微管稳定埃坡霉素可实现细胞骨架动力学的时空控制


细胞骨架对于各种细胞和组织水平过程的空间和时间组织至关重要，例如增殖、信号传导、货物运输、迁移、形态发生和神经元发育。细胞骨架研究旨在通过成像或局部操纵具有高时空分辨率的细胞骨架蛋白的动力学和组织来研究这些过程：这与光学方法的能力相匹配。迄今为止，还没有一种光响应微管稳定工具能够结合实用高精度试剂所需的所有功能：低效和生化稳定的非照明状态；然后高效、快速、干净的光响应，产生高效能的照明状态；加上在合适的工作浓度下良好的溶解度；和高效的合成访问。我们现在推出 CouEpo，一种结合了这些需求的光笼埃坡霉素微管稳定试剂。在紫/蓝色照射下，其效力增加约 100 倍，达到低纳摩尔值，从而可以有效地光控制活细胞中的微管动力学，甚至可以产生微管结构和细胞动力学中的细胞不对称性。因此，CouEpo 是一种高性能工具化合物，可以支持从生物物理学到运输、细胞运动和神经元生理学等许多微管相关过程的高精度研究。