2026年9月5日，美国加利福尼亚大学Bo Huang等科学家在《细胞》发表研究，报道了从头设计的泛罗丹明结合蛋白（Rhobin），实现了从哺乳动物细胞到极端微生物的荧光成像。
活细胞荧光成像是生命科学的基石。虽然天然荧光蛋白已被工程化改造以增强个体特性，但现有标签尚无能将理想特性整合到单一系统中：高亮度、可逆结合、尺寸紧凑以及跨多种条件的稳定性。在此，研究人员通过从头设计罗丹明结合蛋白（Rhobin）实现了这一目标。为了利用罗丹明荧光团的广泛谱系，他们开发了一种适用于不同波长和应用的泛罗丹明结合蛋白通用设计策略。Rhobin能够对哺乳动物细胞中多种亚细胞靶标进行活细胞和固定细胞成像，其亮度超过现有标签。其可逆荧光团结合支持超分辨受激发射损耗（STED）成像，并且与HaloTag相比可延长活细胞单分子成像的持续时间。超越传统系统，Rhobin还实现了极端微生物Sulfolobus acidocaldarius在75°C下的活细胞成像，这在现有标签中是无法实现的。总之，这些结果确立了Rhobin作为下一代成像和生物传感器设计的多功能平台。
附：英文原文
Title: De novo pan-rhodamine binders for fluorescence microscopy from mammalian cells to extremophiles
Author: Yuda Chen, Klaus Yserentant, Kibeom Hong, Kehan Chen, Yiming Kuang, Robert S. Picardo, Arghya Bhowmick, Arthur Charles-Orszag, Samuel J. Lord, Lei Lu, Kaipeng Hou, Samuel I. Mann, Sagar Bhattacharya, Maggie Horst, Jonathan B. Grimm, Luke D. Lavis, R. Dyche Mullins, William F. DeGrado, Bo Huang
Issue&Volume:
Abstract: Fluorescent imaging in live cells is a cornerstone of life sciences. While natural fluorescent proteins have been engineered to enhance individual features, no existing tag combines ideal properties into a single system: high brightness, reversible binding, compact size, and stability across diverse conditions. Here, we achieve this through de novo design of rhodamine binders (Rhobin). To harness the broad repertoire of rhodamine fluorophores, we developed a generalizable design strategy for a pan-rhodamine binder compatible with diverse wavelengths and applications. Rhobin enables live- and fixed-cell imaging of various subcellular targets in mammalian cells, showing brightness surpassing existing tags. Its reversible fluorophore binding supports super-resolution stimulated emission depletion (STED) and live-cell single-molecule imaging for extended durations compared with HaloTag. Beyond conventional systems, Rhobin enables live imaging of the extremophile Sulfolobus acidocaldarius at 75°C, previously inaccessible with current tags. Together, these results establish Rhobin as a versatile platform for next-generation imaging and biosensor design.
DOI: 10.1016/j.cell.2026.08.007
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00934-7