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Toward high-throughput biomechanical phenotyping of single molecules

Nature Methods volume 12, pages 45–46 (2015)Cite this article

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Two high-throughput single-molecule force spectroscopy platforms expand the reach of this technology for biomechanical molecular phenotyping.

Single-molecule force spectroscopy (SMFS) is a powerful tool for mechanical manipulation of single biomolecules such as DNA, RNA, sugars, proteins and lipids. Typically, a molecule of interest attached to a surface at one end is pulled from the other end using a highly precise force-transducing device while the molecular response is recorded. Through this manipulation it is possible to determine structural, mechanical and adhesive properties of biomolecules, as well as to observe their folding and misfolding pathways or approximate their thermodynamic and kinetic parameters. It is even possible to determine and mechanically control the functional state of single proteins or to characterize how this state interacts with drugs or other functional biomolecules. This has opened an exciting avenue toward manipulating and understanding biomolecular systems in vitro and in vivo. Nevertheless, the widespread use of single-molecule methods has been hampered by their low experimental throughput. Two recent papers published in Nature Methods give general guidelines for the design, optimization and validation of high-throughput SMFS. If combined, these techniques could open the door to a new bioanalytical dimension through highly parallelized and accurate measurements of the biomechanical phenotypes of thousands of proteins1,2.

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Authors and Affiliations

  1. Savaş Tay and Daniel J Müller are in the Department of Biosystems Science and Engineering, David Alsteens, ETH Zürich, Basel, Switzerland.,

    David Alsteens, Savaş Tay & Daniel J Müller

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  1. David Alsteens
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  2. Savaş Tay
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  3. Daniel J Müller
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Correspondence to Daniel J Müller.

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The authors declare no competing financial interests.

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Alsteens, D., Tay, S. & Müller, D. Toward high-throughput biomechanical phenotyping of single molecules. Nat Methods 12, 45–46 (2015). https://doi.org/10.1038/nmeth.3216

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