Department of Chemistry, Purdue University, 560 Oval Dr., West Lafayette, IN, 47907, USA.
Purdue Center for Cancer Research, 201 S. University St., West Lafayette, IN, 47907, USA.
Nat Commun. 2022 Jul 27;13(1):4343. doi: 10.1038/s41467-022-32071-z.
Precision control of molecular activities and chemical reactions in live cells is a long-sought capability by life scientists. No existing technology can probe molecular targets in cells and simultaneously control the activities of only these targets at high spatial precision. We develop a real-time precision opto-control (RPOC) technology that detects a chemical-specific optical response from molecular targets during laser scanning and uses the optical signal to couple a separate laser to only interact with these molecules without affecting other sample locations. We demonstrate precision control of molecular states of a photochromic molecule in different regions of the cells. We also synthesize a photoswitchable compound and use it with RPOC to achieve site-specific inhibition of microtubule polymerization and control of organelle dynamics in live cells. RPOC can automatically detect and control biomolecular activities and chemical processes in dynamic living samples with submicron spatial accuracy, fast response time, and high chemical specificity.
活细胞中分子活动和化学反应的精确控制是生命科学家长期追求的目标。目前尚无技术能够在探测细胞内分子靶标时，同时以高空间精度仅控制这些靶标的活性。我们开发了一种实时精密光控（RPOC）技术，该技术可在激光扫描过程中检测到分子靶标特有的光化学响应，并利用该光学信号将单独的激光耦合到仅与这些分子相互作用，而不会影响其他样品位置。我们展示了在细胞的不同区域对光致变色分子的分子状态进行精确控制。我们还合成了一种光致开关化合物，并将其与 RPOC 一起用于实现微管聚合的特异性抑制以及活细胞中细胞器动力学的控制。RPOC 可以自动检测和控制具有亚微米空间精度、快速响应时间和高化学特异性的动态活样本中的生物分子活性和化学过程。
