ArticleProceedings of the National Academy of Sciences of the United States of America2016
Directly measuring single-molecule heterogeneity using force spectroscopy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Force writes memory: proline isomerization as a molecular memory switch.Biochemical Society transactions · 2025Review
- Different folding mechanisms in prion proteins from mammals with different disease susceptibility observed at the single-molecule level.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identical sequences, different behaviors: Protein diversity captured at the single-molecule level.Biophysical journal · 2024Article
- Catch bonds in sickle cell disease: Shear-enhanced adhesion of red blood cells to laminin.Biophysical journal · 2023Article
- Moderate activity of RNA chaperone maximizes the yield of self-spliced pre-RNA in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Unfolded and intermediate states of PrP play a key role in the mechanism of action of an antiprion chaperone.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Biological physics by high-speed atomic force microscopy.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2020Review
- Dynamic coordination of two-metal-ions orchestrates λ-exonuclease catalysis.Nature communications · 2018Article
- Unraveling the mechanism of the cadherin-catenin-actin catch bond.PLoS computational biology · 2018Article
- Fodis: Software for Protein Unfolding Analysis.Biophysical journal · 2018Article
- Elucidating distinct ion channel populations on the surface of hippocampal neurons via single-particle tracking recurrence analysis.Physical review. E · 2017Article
- Heterogeneity in kinesin function.Traffic (Copenhagen, Denmark) · 2017Article
- Decoding Single Molecule Time Traces with Dynamic Disorder.PLoS computational biology · 2016Article
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3 authors.
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Abstract
One of the most intriguing results of single-molecule experiments on proteins and nucleic acids is the discovery of functional heterogeneity: the observation that complex cellular machines exhibit multiple, biologically active conformations. The structural differences between these conformations may be subtle, but each distinct state can be remarkably long-lived, with interconversions between states occurring only at macroscopic timescales, fractions of a second or longer. Although we now have proof of functional heterogeneity in a handful of systems-enzymes, motors, adhesion complexes-identifying and measuring it remains a formidable challenge. Here, we show that evidence of this phenomenon is more widespread than previously known, encoded in data collected from some of the most well-established single-molecule techniques: atomic force microscopy or optical tweezer pulling experiments. We present a theoretical procedure for analyzing distributions of rupture/unfolding forces recorded at different pulling speeds. This results in a single parameter, quantifying the degree of heterogeneity, and also leads to bounds on the equilibration and conformational interconversion timescales. Surveying 10 published datasets, we find heterogeneity in 5 of them, all with interconversion rates slower than 10 s(-1) Moreover, we identify two systems where additional data at realizable pulling velocities is likely to find a theoretically predicted, but so far unobserved crossover regime between heterogeneous and nonheterogeneous behavior. The significance of this regime is that it will allow far more precise estimates of the slow conformational switching times, one of the least understood aspects of functional heterogeneity.
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