Nanotechnology: flexible biosensors with modular design
Researchers have developed a strategy that enables biosensors to be easily adapted for a wide range of applications.
© LMU
The sensor uses a DNA origami scaffold, which consists of two arms connected by a molecular “hinge.” Each arm is tagged with a fluorescent dye, and the distance between the tags is recorded by means of fluorescence resonance energy transfer (FRET). In a closed state, the two arms are parallel; when the structure opens, the arms fold out to form an angle of up to 90°. “As a result of this large conformational change, the fluorescence signal also changes substantially,” explains Viktorija Glembockyte, senior author of the study. “This allows signals to be measured with considerably greater clarity and precision than in systems with small conformational changes.”
Cooperative effects
The origami scaffold can be equipped with docking sites for various biomolecular targets such as nucleic acids, antibodies, and proteins. Whether the sensor is open or closed depends on the binding of the respective target molecule to the origami scaffold. The sensor can thus be deliberately adapted and optimized through the use of additional binding sites or stabilizing DNA strands. “It’s relatively easy to design the origami such that several molecular interactions between target molecule and sensor are queried simultaneously,” explains Tinnefeld. “These multiple bonds lead to interesting cooperative effects which make it possible to specifically control the sensitivity of the sensor without intervening in the biomolecular interactions themselves – that is to say, the strength with which the target molecule docks to its binding site. This flexibility is a major advantage of our system.”
The researchers plan to further optimize the sensor in the future for biomedical and other applications. A possible field of application could be sensors that monitor various parameters and release active agents under certain conditions, says Tinnefeld.
Original publication
Lennart Grabenhorst, Martina Pfeiffer, Thea Schinkel, Mirjam Kümmerlin, Gereon A. Brüggenthies, Jasmin B. Maglic, Florian Selbach, Alexander T. Murr, Philip Tinnefeld, Viktorija Glembockyte; "Engineering modular and tunable single-molecule sensors by decoupling sensing from signal output"; Nature Nanotechnology, 2024-11-7
Original publication
Lennart Grabenhorst, Martina Pfeiffer, Thea Schinkel, Mirjam Kümmerlin, Gereon A. Brüggenthies, Jasmin B. Maglic, Florian Selbach, Alexander T. Murr, Philip Tinnefeld, Viktorija Glembockyte; "Engineering modular and tunable single-molecule sensors by decoupling sensing from signal output"; Nature Nanotechnology, 2024-11-7
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