Center for Integrated Nanotechnologies , Sandia National Laboratories , P.O. Box 5800, MS 1303, Albuquerque , New Mexico 87185 , United States.
Biomacromolecules. 2018 Jul 9;19(7):2401-2408. doi: 10.1021/acs.biomac.7b01799. Epub 2018 Apr 30.
Microtubule dynamics play a critical role in the normal physiology of eukaryotic cells as well as a number of cancers and neurodegenerative disorders. The polymerization/depolymerization of microtubules is regulated by a variety of stabilizing and destabilizing factors, including microtubule-associated proteins and therapeutic agents (e.g., paclitaxel, nocodazole). Here we describe the ability of the osmolytes polyethylene glycol (PEG) and trimethylamine- N-oxide (TMAO) to inhibit the depolymerization of individual microtubule filaments for extended periods of time (up to 30 days). We further show that PEG stabilizes microtubules against both temperature- and calcium-induced depolymerization. Our results collectively suggest that the observed inhibition may be related to combination of the kosmotropic behavior and excluded volume/osmotic pressure effects associated with PEG and TMAO. Taken together with prior studies, our data suggest that the physiochemical properties of the local environment can regulate microtubule depolymerization and may potentially play an important role in in vivo microtubule dynamics.
微管动力学在真核细胞的正常生理学以及许多癌症和神经退行性疾病中起着关键作用。微管的聚合/解聚受多种稳定和不稳定因素的调节，包括微管相关蛋白和治疗剂（如紫杉醇、诺考达唑）。在这里，我们描述了渗透剂聚乙二醇（PEG）和三甲胺 N-氧化物（TMAO）能够在较长时间内（长达 30 天）抑制单个微管丝的解聚的能力。我们进一步表明，PEG 可以稳定微管，防止其因温度和钙诱导而解聚。我们的结果表明，观察到的抑制可能与 PEG 和 TMAO 相关的亲水性行为和排除体积/渗透压效应的组合有关。结合之前的研究，我们的数据表明，局部环境的物理化学性质可以调节微管的解聚，并且可能在体内微管动力学中发挥重要作用。
