Krasley Andrew T, Chakraborty Sayantani, Vuković Lela, Beyene Abraham G
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, United States.
Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, Texas 79968, United States.
ACS Nano. 2025 Mar 4;19(8):7804-7820. doi: 10.1021/acsnano.4c13814. Epub 2025 Jan 16.
Most traditional optical biosensors operate through molecular recognition, where ligand binding causes conformational changes that lead to optical perturbations in the emitting motif. Optical sensors developed from single-stranded DNA-functionalized single-walled carbon nanotubes (ssDNA-SWCNTs) have started to make useful contributions to biological research. However, the mechanisms underlying their function have remained poorly understood. In this study, we combine experimental and computational approaches to show that ligand binding alone is not sufficient for optical modulation in this class of synthetic biosensors. Instead, the optical response that occurs after ligand binding is highly dependent on the chemical properties of the ligands, resembling mechanisms seen in activity-based biosensors. Specifically, we show that in ssDNA-SWCNT catecholamine sensors, the optical response correlates positively with the electron density on the aryl motif, even among ligands with similar ligand binding affinities. Importantly, despite the strong correlations with electrochemical properties, we find that catechol oxidation itself is not necessary to drive the sensor optical response. We discuss how these findings could serve as a framework for tuning the performance of existing sensors and guiding the development of new biosensors of this class.
大多数传统光学生物传感器通过分子识别发挥作用，其中配体结合会引起构象变化，进而导致发射基序中的光学扰动。由单链DNA功能化的单壁碳纳米管（ssDNA-SWCNTs）开发的光学传感器已开始对生物学研究做出有益贡献。然而，其功能背后的机制仍知之甚少。在本研究中，我们结合实验和计算方法表明，在这类合成生物传感器中，仅配体结合不足以实现光学调制。相反，配体结合后发生的光学响应高度依赖于配体的化学性质，类似于基于活性的生物传感器中的机制。具体而言，我们表明，在ssDNA-SWCNT儿茶酚胺传感器中，即使在具有相似配体结合亲和力的配体中，光学响应也与芳基基序上的电子密度呈正相关。重要的是，尽管与电化学性质有很强的相关性，但我们发现儿茶酚氧化本身并非驱动传感器光学响应所必需的。我们讨论了这些发现如何能够作为一个框架，用于调整现有传感器的性能并指导此类新型生物传感器的开发。
