A multimodal, correlative magnetic tweezers-TIRF platform for high-throughput single-molecule interrogations

Authors

Feiz, M. S., Cnossen, J., Wubulikasimu, Y., Quack, S., Bugea, T., Zupnik, A., Prajapati, R. K., Rakib, A., Papini, F. S., Smitskamp, Q., Malinen, A., Dulin, D.

Abstract

Single-molecule techniques can resolve biological reactions at unmatched detail, but their low throughput and single-modality readouts have kept them out of data-intensive pipelines such as omics and drug discovery, and beyond reach of low-yield biological systems. Here we introduce a multimodal platform integrating high-throughput magnetic tweezers with ultra-wide- and flat-field objective-based total internal reflection fluorescence, enabling simultaneous force, torque, multicolor fluorescence, and temperature-dependent measurements on up to thousands of individual molecules in parallel and in real time. We demonstrate accurate single-molecule Foerster resonance energy transfer (smFRET) for prism-based spectral imaging, capture temperature-dependent hairpin folding dynamics at high temporal resolution with smFRET and use correlative torque-fluorescence measurements to unravel the open-complex formation dynamics during bacterial transcription initiation. By unifying high resolution, throughput, and multimodal readout, this platform enables multidimensional dissection of complex biomolecular reactions with high statistical confidence, unlocking single-molecule biophysics for integration with drug discovery, omics, and cryo-EM workflows.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 18 Aug 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.