DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Mapping mechanical force propagation through biomolecular complexes

Abstract

In this paper, we employ single-molecule force spectroscopy with an atomic force microscope (AFM) and steered molecular dynamics (SMD) simulations to reveal force propagation pathways through a mechanically ultrastable multidomain cellulosome protein complex. We demonstrate a new combination of network-based correlation analysis supported by AFM directional pulling experiments, which allowed us to visualize stiff paths through the protein complex along which force is transmitted. Finally, the results implicate specific force-propagation routes nonparallel to the pulling axis that are advantageous for achieving high dissociation forces.

Authors:
 [1];  [2];  [1];  [1];  [3];  [4];  [2];  [1];  [1]
  1. Ludwig-Maximilians-Univ., Munich (Germany)
  2. Univ. of Illinois at Urbana-Champaign, Urbana, IL (United States)
  3. Ludwig-Maximilians-Univ., Munich (Germany); Univ. of Munich, Munich (Germany)
  4. The Weizmann Institute of Science, Rehovot (Israel)
Publication Date:
Research Org.:
Univ. of Illinois at Urbana-Champaign, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1345019
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Nano Letters
Additional Journal Information:
Journal Volume: 15; Journal Issue: 11; Journal ID: ISSN 1530-6984
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; cohesin−dockerin; force propagation; network analysis; single molecule force spectroscopy; steered molecular dynamics

Citation Formats

Schoeler, Constantin, Bernardi, Rafael C., Malinowska, Klara H., Durner, Ellis, Ott, Wolfgang, Bayer, Edward A., Schulten, Klaus, Nash, Michael A., and Gaub, Hermann E. Mapping mechanical force propagation through biomolecular complexes. United States: N. p., 2015. Web. doi:10.1021/acs.nanolett.5b02727.
Schoeler, Constantin, Bernardi, Rafael C., Malinowska, Klara H., Durner, Ellis, Ott, Wolfgang, Bayer, Edward A., Schulten, Klaus, Nash, Michael A., & Gaub, Hermann E. Mapping mechanical force propagation through biomolecular complexes. United States. https://doi.org/10.1021/acs.nanolett.5b02727
Schoeler, Constantin, Bernardi, Rafael C., Malinowska, Klara H., Durner, Ellis, Ott, Wolfgang, Bayer, Edward A., Schulten, Klaus, Nash, Michael A., and Gaub, Hermann E. Tue . "Mapping mechanical force propagation through biomolecular complexes". United States. https://doi.org/10.1021/acs.nanolett.5b02727. https://www.osti.gov/servlets/purl/1345019.
@article{osti_1345019,
title = {Mapping mechanical force propagation through biomolecular complexes},
author = {Schoeler, Constantin and Bernardi, Rafael C. and Malinowska, Klara H. and Durner, Ellis and Ott, Wolfgang and Bayer, Edward A. and Schulten, Klaus and Nash, Michael A. and Gaub, Hermann E.},
abstractNote = {In this paper, we employ single-molecule force spectroscopy with an atomic force microscope (AFM) and steered molecular dynamics (SMD) simulations to reveal force propagation pathways through a mechanically ultrastable multidomain cellulosome protein complex. We demonstrate a new combination of network-based correlation analysis supported by AFM directional pulling experiments, which allowed us to visualize stiff paths through the protein complex along which force is transmitted. Finally, the results implicate specific force-propagation routes nonparallel to the pulling axis that are advantageous for achieving high dissociation forces.},
doi = {10.1021/acs.nanolett.5b02727},
journal = {Nano Letters},
number = 11,
volume = 15,
place = {United States},
year = {Tue Aug 11 00:00:00 EDT 2015},
month = {Tue Aug 11 00:00:00 EDT 2015}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 58 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Cell and molecular mechanics of biological materials
journal, November 2003


Cartilage Tissue Remodeling in Response to Mechanical Forces
journal, August 2000


Mechanics, malignancy, and metastasis: The force journey of a tumor cell
journal, January 2009


Stretching Single Talin Rod Molecules Activates Vinculin Binding
journal, January 2009


Single-Molecule Experiments in Vitro and in Silico
journal, May 2007


In Situ Atomic Force Microscopy as a Tool for Investigating Interactions and Assembly Dynamics in Biomolecular and Biomineral Systems
journal, April 2013

  • De Yoreo, James J.; Chung, Sungwook; Friddle, Raymond W.
  • Advanced Functional Materials, Vol. 23, Issue 20
  • DOI: 10.1002/adfm.201203424

The Mechanical Stability of Immunoglobulin and Fibronectin III Domains in the Muscle Protein Titin Measured by Atomic Force Microscopy
journal, December 1998


Reversible Unfolding of Individual Titin Immunoglobulin Domains by AFM
journal, May 1997


The Molecular Mechanism Underlying Mechanical Anisotropy of the Protein GB1
journal, December 2012

  • Li, Yongnan Devin; Lamour, Guillaume; Gsponer, Jörg
  • Biophysical Journal, Vol. 103, Issue 11
  • DOI: 10.1016/j.bpj.2012.10.035

Mechanical Anisotropy of Ankyrin Repeats
journal, March 2012


Direct observation of a force-induced switch in the anisotropic mechanical unfolding pathway of a protein
journal, September 2012

  • Jagannathan, B.; Elms, P. J.; Bustamante, C.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 44
  • DOI: 10.1073/pnas.1201800109

Anisotropic deformation response of single protein molecules
journal, August 2006

  • Dietz, H.; Berkemeier, F.; Bertz, M.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 34
  • DOI: 10.1073/pnas.0602995103

The mechanical stability of ubiquitin is linkage dependent
journal, August 2003

  • Carrion-Vazquez, Mariano; Li, Hongbin; Lu, Hui
  • Nature Structural & Molecular Biology, Vol. 10, Issue 9
  • DOI: 10.1038/nsb965

Pulling geometry defines the mechanical resistance of a β-sheet protein
journal, August 2003

  • Brockwell, David J.; Paci, Emanuele; Zinober, Rebecca C.
  • Nature Structural & Molecular Biology, Vol. 10, Issue 9
  • DOI: 10.1038/nsb968

Nanomechanics of HaloTag Tethers
journal, August 2013

  • Popa, Ionel; Berkovich, Ronen; Alegre-Cebollada, Jorge
  • Journal of the American Chemical Society, Vol. 135, Issue 34
  • DOI: 10.1021/ja4056382

Molecular dynamics simulations of large macromolecular complexes
journal, April 2015

  • Perilla, Juan R.; Goh, Boon Chong; Cassidy, C. Keith
  • Current Opinion in Structural Biology, Vol. 31
  • DOI: 10.1016/j.sbi.2015.03.007

Enhanced sampling techniques in molecular dynamics simulations of biological systems
journal, May 2015

  • Bernardi, Rafael C.; Melo, Marcelo C. R.; Schulten, Klaus
  • Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1850, Issue 5
  • DOI: 10.1016/j.bbagen.2014.10.019

Energy Propagation and Network Energetic Coupling in Proteins
journal, January 2015

  • Ribeiro, Andre A. S. T.; Ortiz, Vanessa
  • The Journal of Physical Chemistry B, Vol. 119, Issue 5
  • DOI: 10.1021/jp509906m

Weighted Implementation of Suboptimal Paths (WISP): An Optimized Algorithm and Tool for Dynamical Network Analysis
journal, January 2014

  • Van Wart, Adam T.; Durrant, Jacob; Votapka, Lane
  • Journal of Chemical Theory and Computation, Vol. 10, Issue 2
  • DOI: 10.1021/ct4008603

Exploring Residue Component Contributions to Dynamical Network Models of Allostery
journal, July 2012

  • VanWart, Adam T.; Eargle, John; Luthey-Schulten, Zaida
  • Journal of Chemical Theory and Computation, Vol. 8, Issue 8
  • DOI: 10.1021/ct300377a

Experimental and computational determination of tRNA dynamics
journal, November 2009


Markov propagation of allosteric effects in biomolecular systems: application to GroEL–GroES
journal, January 2006

  • Chennubhotla, Chakra; Bahar, Ivet
  • Molecular Systems Biology, Vol. 2, Issue 1
  • DOI: 10.1038/msb4100075

How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism
journal, February 2008


Molecular dynamics simulations of membrane channels and transporters
journal, April 2009

  • Khalili-Araghi, Fatemeh; Gumbart, James; Wen, Po-Chao
  • Current Opinion in Structural Biology, Vol. 19, Issue 2
  • DOI: 10.1016/j.sbi.2009.02.011

Exploring coumarin egress channels in human cytochrome p450 2a6 by random acceleration and steered molecular dynamics simulations
journal, November 2010

  • Li, Weihua; Shen, Jie; Liu, Guixia
  • Proteins: Structure, Function, and Bioinformatics, Vol. 79, Issue 1
  • DOI: 10.1002/prot.22880

Ultrastable cellulosome-adhesion complex tightens under load
journal, December 2014

  • Schoeler, Constantin; Malinowska, Klara H.; Bernardi, Rafael C.
  • Nature Communications, Vol. 5, Issue 1
  • DOI: 10.1038/ncomms6635

Mechanical Network in Titin Immunoglobulin from Force Distribution Analysis
journal, March 2009


Mechanical Response of Silk Crystalline Units from Force-Distribution Analysis
journal, May 2009


Implementation of force distribution analysis for molecular dynamics simulations
journal, January 2011

  • Stacklies, Wolfram; Seifert, Christian; Graeter, Frauke
  • BMC Bioinformatics, Vol. 12, Issue 1
  • DOI: 10.1186/1471-2105-12-101

Force Distribution Reveals Signal Transduction in E. coli Hsp90
journal, November 2012


An Allosteric Signaling Pathway of Human 3-Phosphoglycerate Kinase from Force Distribution Analysis
journal, January 2014


Atypical Cohesin-Dockerin Complex Responsible for Cell Surface Attachment of Cellulosomal Components
journal, June 2013

  • Salama-Alber, Orly; Jobby, Maroor K.; Chitayat, Seth
  • Journal of Biological Chemistry, Vol. 288, Issue 23
  • DOI: 10.1074/jbc.M113.466672

Comparing Proteins by Their Unfolding Pattern
journal, July 2008


Interpreting the widespread nonlinear force spectra of intermolecular bonds
journal, August 2012

  • Friddle, R. W.; Noy, A.; De Yoreo, J. J.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 34
  • DOI: 10.1073/pnas.1202946109

Intrinsic Rates and Activation Free Energies from Single-Molecule Pulling Experiments
journal, March 2006


On the Formalism of Thermodynamic Fluctuation Theory
journal, September 1951


Scalable molecular dynamics with NAMD
journal, January 2005

  • Phillips, James C.; Braun, Rosemary; Wang, Wei
  • Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802
  • DOI: 10.1002/jcc.20289

Dynamical networks in tRNA:protein complexes
journal, April 2009

  • Sethi, A.; Eargle, J.; Black, A. A.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 16
  • DOI: 10.1073/pnas.0810961106

From genes to protein mechanics on a chip
journal, September 2014

  • Otten, Marcus; Ott, Wolfgang; Jobst, Markus A.
  • Nature Methods, Vol. 11, Issue 11
  • DOI: 10.1038/nmeth.3099

Single-molecule dissection of the high-affinity cohesin-dockerin complex
journal, November 2012

  • Stahl, S. W.; Nash, M. A.; Fried, D. B.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 50
  • DOI: 10.1073/pnas.1211929109

Investigating Receptor-ligand Systems of the Cellulosome with AFM-based Single-molecule Force Spectroscopy
journal, January 2013

  • Jobst, Markus A.; Schoeler, Constantin; Malinowska, Klara
  • Journal of Visualized Experiments, Issue 82
  • DOI: 10.3791/50950

Mechanostability of cohesin-dockerin complexes in a structure-based model: Anisotropy and lack of universality in the force profiles
journal, December 2014

  • Wojciechowski, Michał; Thompson, Damien; Cieplak, Marek
  • The Journal of Chemical Physics, Vol. 141, Issue 24
  • DOI: 10.1063/1.4904726

A Network of Conserved Interactions Regulates the Allosteric Signal in a Glutamine Amidotransferase
journal, February 2007

  • Amaro, Rommie E.; Sethi, Anurag; Myers, Rebecca S.
  • Biochemistry, Vol. 46, Issue 8
  • DOI: 10.1021/bi061708e

VMD: Visual molecular dynamics
journal, February 1996


Works referencing / citing this record:

Cellulosomes: bacterial nanomachines for dismantling plant polysaccharides
journal, December 2016

  • Artzi, Lior; Bayer, Edward A.; Moraïs, Sarah
  • Nature Reviews Microbiology, Vol. 15, Issue 2
  • DOI: 10.1038/nrmicro.2016.164

Amino acid modified carbon nanotubes with optimal pore size for chiral separation
journal, June 2019


Broken force dispersal network in tip-links by the mutations induces hearing-loss
journal, April 2019

  • Hazra, Jagadish P.; Sagar, Amin; Arora, Nisha
  • Biochemical Journal
  • DOI: 10.1101/614610

A modular DNA scaffold to study protein–protein interactions at single-molecule resolution
journal, September 2019

  • Kostrz, Dorota; Wayment-Steele, Hannah K.; Wang, Jing L.
  • Nature Nanotechnology, Vol. 14, Issue 10
  • DOI: 10.1038/s41565-019-0542-7

Molecular mechanism of extreme mechanostability in a pathogen adhesin
journal, March 2018


Steered molecular dynamics simulations reveal the role of Ca 2+ in regulating mechanostability of cellulose-binding proteins
journal, January 2018

  • Gunnoo, Melissabye; Cazade, Pierre-André; Orlowski, Adam
  • Physical Chemistry Chemical Physics, Vol. 20, Issue 35
  • DOI: 10.1039/c8cp00925b

NAMD goes quantum: an integrative suite for hybrid simulations
journal, March 2018

  • Melo, Marcelo C. R.; Bernardi, Rafael C.; Rudack, Till
  • Nature Methods, Vol. 15, Issue 5
  • DOI: 10.1038/nmeth.4638

Dynamic interactions of type I cohesin modules fine-tune the structure of the cellulosome of Clostridium thermocellum
journal, May 2018

  • Barth, Anders; Hendrix, Jelle; Fried, Daniel
  • Proceedings of the National Academy of Sciences
  • DOI: 10.1101/328088

QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts
journal, May 2016

  • Ribeiro, João V.; Bernardi, Rafael C.; Rudack, Till
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep26536

High Force Catch Bond Mechanism of Bacterial Adhesion in the Human Gut
journal, January 2020


Enzyme-Mediated, Site-Specific Protein Coupling Strategies for Surface-Based Binding Assays
journal, August 2018

  • Ott, Wolfgang; Durner, Ellis; Gaub, Hermann E.
  • Angewandte Chemie, Vol. 130, Issue 39
  • DOI: 10.1002/ange.201805034

Atomic force microscopy-based mechanobiology
journal, November 2018

  • Krieg, Michael; Fläschner, Gotthold; Alsteens, David
  • Nature Reviews Physics, Vol. 1, Issue 1
  • DOI: 10.1038/s42254-018-0001-7

Dynamic interactions of type I cohesin modules fine-tune the structure of the cellulosome of Clostridium thermocellum
journal, November 2018

  • Barth, Anders; Hendrix, Jelle; Fried, Daniel
  • Proceedings of the National Academy of Sciences, Vol. 115, Issue 48
  • DOI: 10.1073/pnas.1809283115

Staphylococcus aureus clumping factor A is a force-sensitive molecular switch that activates bacterial adhesion
journal, May 2018

  • Herman-Bausier, Philippe; Labate, Cristina; Towell, Aisling M.
  • Proceedings of the National Academy of Sciences, Vol. 115, Issue 21
  • DOI: 10.1073/pnas.1718104115

Steering chemical reactions with force
journal, November 2017


Mechanical Polyprotein Assembly Using Sfp and Sortase-Mediated Domain Oligomerization for Single-Molecule Studies
journal, May 2018


Broken force dispersal network in tip-links by the mutations at the Ca2+-binding residues induces hearing-loss
journal, August 2019

  • Hazra, Jagadish P.; Sagar, Amin; Arora, Nisha
  • Biochemical Journal, Vol. 476, Issue 16
  • DOI: 10.1042/bcj20190453

Enzyme-Mediated, Site-Specific Protein Coupling Strategies for Surface-Based Binding Assays
journal, August 2018

  • Ott, Wolfgang; Durner, Ellis; Gaub, Hermann E.
  • Angewandte Chemie International Edition, Vol. 57, Issue 39
  • DOI: 10.1002/anie.201805034

High force catch bond mechanism of bacterial adhesion in the human gut
text, January 2020


Amino acid modified carbon nanotubes with optimal pore size for chiral separation
text, January 2019


Amino acid modified carbon nanotubes with optimal pore size for chiral separation
text, January 2019


High force catch bond mechanism of bacterial adhesion in the human gut
text, January 2020


High force catch bond mechanism of bacterial adhesion in the human gut
journal, August 2020


Steered molecular dynamics simulations reveal the role of Ca2+ in regulating mechanostability of cellulose-binding proteins
text, January 2018

  • Melissabye, Gunnoo,; Pierre-André, Cazade,; Adam, Orlowski,
  • Royal Society of Chemistry
  • DOI: 10.5451/unibas-ep67937

Removal of a Conserved Disulfide Bond Does Not Compromise Mechanical Stability of a VHH Antibody Complex
journal, July 2019


Skeletal Dysplasia Mutations Effect on Human Filamins’ Structure and Mechanosensing
journal, June 2017


QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts
journal, May 2016

  • Ribeiro, João V.; Bernardi, Rafael C.; Rudack, Till
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep26536

Broken force dispersal network in tip-links by the mutations at the Ca2+-binding residues induces hearing-loss
journal, August 2019

  • Hazra, Jagadish P.; Sagar, Amin; Arora, Nisha
  • Biochemical Journal, Vol. 476, Issue 16
  • DOI: 10.1042/bcj20190453

Streptavidin/biotin: Tethering geometry defines unbinding mechanics
journal, March 2020

  • Sedlak, Steffen M.; Schendel, Leonard C.; Gaub, Hermann E.
  • Science Advances, Vol. 6, Issue 13
  • DOI: 10.1126/sciadv.aay5999

Force-Induced Strengthening of the Interaction between Staphylococcus aureus Clumping Factor B and Loricrin
journal, December 2017


Mechanisms of Nanonewton Mechanostability in a Protein Complex Revealed by Molecular Dynamics Simulations and Single-Molecule Force Spectroscopy
text, January 2019

  • C., Bernardi, Rafael; Ellis, Durner,; Constantin, Schoeler,
  • American Chemical Society
  • DOI: 10.5451/unibas-ep72178