Biophysical Society Thematic Meeting | Tutzing 2026

Single-Molecule FRET: The Next 30 Years

Thursday Speaker Abstracts

PROGRAMMING FRET: ENGINEERING PRECISE INTERACTIONS FOR MODULAR SENSING AND SUPERRESOLUTION IMAGING Viktorija Glembockyte 1 ; 1 Max Planck Institute for Medical Research, Heidelberg, Germany Thirty years on, FRET remains one of the most versatile readouts in single-molecule fluorescence. Here I will discuss how precisely engineered, DNA-mediated interactions allow us to use it not only to report on molecular processes, but to program them by design. We will first present a modular single-molecule sensor platform based on dynamic DNA origami nanostructures, in which the sensing event is decoupled from the signal output [1]. This separation allows us to engineer a high FRET signal response once and then independently tune the response window, specificity and cooperativity of the sensor, while exchanging the recognition element to address different biomolecular targets — from nucleic acids and proteins to antibodies and more complex, Cas9-based detection schemes. In the second part, I will turn to a different application of DNA-mediated control — this time over the photophysics of the fluorescent label itself. We have developed a fully tunable, background-free photoswitching strategy for single-molecule localization microscopy that relies on programmed interactions in the immediate environment of the dye rather than on fluorescently labelled additives. This offers precise control over the switching kinetics and, with it, over the speed of SMLM acquisition, opening new possibilities for high-performance super-resolution imaging. References: [1] Grabenhorst, L. et al. Nat. Nanotechnol. 2025, 20, 303–310.

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