Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand Complexes

Single-molecule force spectroscopy with the atomic force microscope provides molecular level insights into protein function, allowing researchers to reconstruct energy landscapes and understand functional mechanisms in biology. With steadily advancing methods, this technique has greatly accelerated...

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Main Authors: Byeongseon Yang, Zhaowei Liu, Haipei Liu, Michael A. Nash
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmolb.2020.00085/full
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author Byeongseon Yang
Byeongseon Yang
Zhaowei Liu
Zhaowei Liu
Haipei Liu
Haipei Liu
Michael A. Nash
Michael A. Nash
author_facet Byeongseon Yang
Byeongseon Yang
Zhaowei Liu
Zhaowei Liu
Haipei Liu
Haipei Liu
Michael A. Nash
Michael A. Nash
author_sort Byeongseon Yang
collection DOAJ
description Single-molecule force spectroscopy with the atomic force microscope provides molecular level insights into protein function, allowing researchers to reconstruct energy landscapes and understand functional mechanisms in biology. With steadily advancing methods, this technique has greatly accelerated our understanding of force transduction, mechanical deformation, and mechanostability within single- and multi-domain polyproteins, and receptor-ligand complexes. In this focused review, we summarize the state of the art in terms of methodology and highlight recent methodological improvements for AFM-SMFS experiments, including developments in surface chemistry, considerations for protein engineering, as well as theory and algorithms for data analysis. We hope that by condensing and disseminating these methods, they can assist the community in improving data yield, reliability, and throughput and thereby enhance the information that researchers can extract from such experiments. These leading edge methods for AFM-SMFS will serve as a groundwork for researchers cognizant of its current limitations who seek to improve the technique in the future for in-depth studies of molecular biomechanics.
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spelling doaj.art-046b1dc55e6d4b36aa65c3eb6570f27d2022-12-21T22:32:27ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2020-05-01710.3389/fmolb.2020.00085537771Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand ComplexesByeongseon Yang0Byeongseon Yang1Zhaowei Liu2Zhaowei Liu3Haipei Liu4Haipei Liu5Michael A. Nash6Michael A. Nash7Department of Chemistry, University of Basel, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Chemistry, University of Basel, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Chemistry, University of Basel, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Chemistry, University of Basel, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandSingle-molecule force spectroscopy with the atomic force microscope provides molecular level insights into protein function, allowing researchers to reconstruct energy landscapes and understand functional mechanisms in biology. With steadily advancing methods, this technique has greatly accelerated our understanding of force transduction, mechanical deformation, and mechanostability within single- and multi-domain polyproteins, and receptor-ligand complexes. In this focused review, we summarize the state of the art in terms of methodology and highlight recent methodological improvements for AFM-SMFS experiments, including developments in surface chemistry, considerations for protein engineering, as well as theory and algorithms for data analysis. We hope that by condensing and disseminating these methods, they can assist the community in improving data yield, reliability, and throughput and thereby enhance the information that researchers can extract from such experiments. These leading edge methods for AFM-SMFS will serve as a groundwork for researchers cognizant of its current limitations who seek to improve the technique in the future for in-depth studies of molecular biomechanics.https://www.frontiersin.org/article/10.3389/fmolb.2020.00085/fullsingle-molecule biophysicsmolecular engineeringAFMprotein stability and foldingmolecular biomechanics
spellingShingle Byeongseon Yang
Byeongseon Yang
Zhaowei Liu
Zhaowei Liu
Haipei Liu
Haipei Liu
Michael A. Nash
Michael A. Nash
Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand Complexes
Frontiers in Molecular Biosciences
single-molecule biophysics
molecular engineering
AFM
protein stability and folding
molecular biomechanics
title Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand Complexes
title_full Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand Complexes
title_fullStr Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand Complexes
title_full_unstemmed Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand Complexes
title_short Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand Complexes
title_sort next generation methods for single molecule force spectroscopy on polyproteins and receptor ligand complexes
topic single-molecule biophysics
molecular engineering
AFM
protein stability and folding
molecular biomechanics
url https://www.frontiersin.org/article/10.3389/fmolb.2020.00085/full
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