Center for Nano Science and Technology, IIT@PoliMi, via Pascoli 70/3, 20133, Milano, Italy.
Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts, 02139, USA.
Sci Rep. 2017 Aug 16;7(1):8477. doi: 10.1038/s41598-017-08541-6.
Selective and rapid regulation of ionic channels is pivotal to the understanding of physiological processes and has a crucial impact in developing novel therapeutic strategies. Transient Receptor Potential (TRP) channels are emerging as essential cellular switches that allow animals to respond to their environment. In particular, the Vanilloid Receptor 1 (TRPV1), besides being involved in the body temperature regulation and in the response to pain, has important roles in several neuronal functions, as cytoskeleton dynamics, injured neurons regeneration, synaptic plasticity. Currently available tools to modulate TRPV1 activity suffer from limited spatial selectivity, do not allow for temporally precise control, and are usually not reversible, thus limiting their application potential. The use of optical excitation would allow for overcoming all these limitations. Here, we propose a novel strategy, based on the use of light-sensitive, conjugated polymers. We demonstrate that illumination of a polymer thin film leads to reliable, robust and temporally precise control of TRPV1 channels. Interestingly, the activation of the channel is due to the combination of two different, locally confined effects, namely the release of thermal energy from the polymer surface and the variation of the local ionic concentration at the cell/polymer interface, both mediated by the polymer photoexcitation.
选择性和快速调节离子通道对于理解生理过程至关重要,并对开发新的治疗策略具有关键影响。瞬时受体电位 (TRP) 通道作为重要的细胞开关,使动物能够对环境做出反应。特别是辣椒素受体 1 (TRPV1),除了参与体温调节和疼痛反应外,在几种神经元功能中也具有重要作用,如细胞骨架动力学、受损神经元再生、突触可塑性。目前可用于调节 TRPV1 活性的工具存在空间选择性有限、无法进行时间精确控制且通常不可逆转等问题,限制了它们的应用潜力。光激发的使用将克服所有这些限制。在这里,我们提出了一种基于使用光敏感共轭聚合物的新策略。我们证明了聚合物薄膜的光照会导致 TRPV1 通道的可靠、稳健和时间精确控制。有趣的是,通道的激活是由于聚合物表面释放热能和聚合物光激发介导的细胞/聚合物界面处局部离子浓度变化这两种不同的、局部受限的效应的组合。