近日，意大利理工大学纳米科学与技术中心的Guglielmo Lanzani&Chiara Bertarelli及其研究团队取得一项新进展。经过不懈努力，他们成功研发用于膜电位光学调制的膜靶向推拉偶氮苯。相关研究成果已于2025年1月1日在国际知名学术期刊《光：科学与应用》上发表。

该研究团队介绍了一系列具有推拉特性的膜靶向偶氮苯化合物（MTs），作为细胞刺激的新工具。这些分子具有水溶性，并能自发地嵌入细胞膜中。在光照下，它们会从反式异构化为顺式，从而改变局部电荷分布，进而刺激细胞反应。具体来说，MTs的光异构化能诱导清晰且可重复的细胞膜去极化。其中，最有前景的分子MTP2得到了深入研究。时间分辨光谱技术提供了对激发态演化的见解，并帮助研究人员全面理解了其异构化反应。

分子动力学模拟揭示了该化合物能自发且稳定地嵌入细胞膜中，而不会显著改变双层膜的厚度。研究人员在多种细胞类型中测试了MTP2，包括HEK293T细胞、原代神经元和心肌细胞，均记录到了稳定的去极化现象。体外模型中观察到的膜电位调制归因于细胞膜内MT偶极矩在光驱动下的调制所导致的膜表面电荷变化。

此外，研究人员开发了一个数学模型，成功捕捉到了光刺激下膜电位的时间演变。尽管这种光诱导的去极化不足以触发动作电位，但其在心脏电生理学中具有潜在应用。利用这些调制器进行的低强度光学刺激可以影响心脏电活动，展现出在破坏和终止心律失常方面的潜在疗效。研究人员预期，MTs方法将在神经科学、生物医学和生物光子学领域找到应用场景，为在不进行基因干预的情况下调制细胞生理提供一种工具。

附：英文原文

Title: Membrane-targeted push-pull azobenzenes for the optical modulation of membrane potential

Author: Sesti, Valentina, Magni, Arianna, Moschetta, Matteo, Florindi, Chiara, Pfeffer, Marlene E., DiFrancesco, Mattia Lorenzo, Guizzardi, Michele, Folpini, Giulia, Sala, Luca, Ritacca, Alessandra Gilda, Campanelli, Beatrice, Moretti, Paola, Patern, Giuseppe Maria, Maragliano, Luca, Tommasini, Matteo, Lodola, Francesco, Colombo, Elisabetta, Benfenati, Fabio, Bertarelli, Chiara, Lanzani, Guglielmo

Issue&Volume: 2025-01-01

Abstract: We introduce a family of membrane-targeted azobenzenes (MTs) with a push-pull character as a new tool for cell stimulation. These molecules are water soluble and spontaneously partition in the cell membrane. Upon light irradiation, they isomerize from trans to cis, changing the local charge distribution and thus stimulating the cell response. Specifically, MTs photoisomerization induces clear and reproducible depolarization. The most promising species, MTP2, was extensively studied. Time-resolved spectroscopy techniques provide insights into the excited state evolution and a complete understanding of its isomerization reaction. Molecular Dynamics simulations reveal the spontaneous and stable partitioning of the compound into the cellular membrane, without significant alterations to the bilayer thickness. MTP2 was tested in different cell types, including HEK293T cells, primary neurons, and cardiomyocytes, and a steady depolarization is always recorded. The observed membrane potential modulation in in-vitro models is attributed to the variation in membrane surface charge, resulting from the light-driven modulation of the MT dipole moment within the cell membrane. Additionally, a developed mathematical model successfully captures the temporal evolution of the membrane potential upon photostimulation. Despite being insufficient for triggering action potentials, the rapid light-induced depolarization holds potential applications, particularly in cardiac electrophysiology. Low-intensity optical stimulation with these modulators could influence cardiac electrical activity, demonstrating potential efficacy in destabilizing and terminating cardiac arrhythmias. We anticipate the MTs approach to find applications in neuroscience, biomedicine, and biophotonics, providing a tool for modulating cell physiology without genetic interventions.

DOI: 10.1038/s41377-024-01669-x

Source: https://www.nature.com/articles/s41377-024-01669-x