Skip to main content
SpringerLink
Log in

Protein Mechanics at the Single-Molecule Level

  • Living reference work entry
  • First Online:
Encyclopedia of Complexity and Systems Science

  • 230 Accesses

Definition of the Subject

Proteins can be considered as machine-like devices that function through complex structural changes in their intra- or intermolecular bonding. Understanding the dynamics of the inner workings of proteins is still one of the major challenges in biology.

Many proteins are nanomachines that use mechanical forces to fulfill a variety of cellular functions from replication to cell adhesion to cell crawling. The nanomachinery involved in these processes (i.e., the internal parts of these bionanomachines) is still poorly understood. Protein mechanics has emerged as a new multidisciplinary field to directly apply and measure mechanical forces through an array of recently developed dynamic techniques for manipulating single molecules both in real time and under physiological conditions. After a decade, this field is still maturing fast, and exciting developments await just around the corner.

AFM (atomic force microscopy) single-molecule force spectroscopy (SMFS) is one...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

Atomic force microscopy (AFM):

A near-field type of microscopy that uses a mechanical force sensor (cantilever) and a nanopositioner to either scan a surface obtaining a topography of the sample (“imaging” configuration) and/or to stretch the sample to obtain a force spectrum (“force spectroscopy” configuration). This acronym is also used throughout the text for the instrument itself, the atomic force microscope.

Bionanomachines:

Nanoscopic structures, usually constituted by protein complexes, which perform most cell functions with a few exceptions like genetic information storage.

Enthalpic elasticity:

Elasticity derived from the breaking of noncovalent bonds after stretching.

Entropic elasticity:

In polymer science, this type of elasticity results from the entropic behavior of monomers in a polymer after its stretching. This recoiling is driven by thermal energy (second principle of thermodynamics) and results in the so-called restoring force.

Functionalization:

Process by which specific chemical groups are added typically to a surface and/or the sample to gain certain control of sample immobilization (attachment, orientation, coverage, etc.).

Hookean spring:

A spring that shows a linear force-extension relationship as is the case of an AFM cantilever.

Mechanical stability:

It can be operationally defined as the amplitude of the highest force peak (F max) observed during the stretching of a single protein molecule using the length-clamp mode of SMFS averaged over many unraveling events. Most proteins show just one force peak.

Molecular chaperons:

Protein complexes that help protein folding and complex assembly. Chaperonins are a well-characterized subclass of chaperons that assist in the folding of newly made proteins in all cells. These bionanomachines use chemical energy in the form of adenosine triphosphate (ATP).

Molecular dynamics:

A specialized discipline of molecular modeling and computer simulation based on statistical mechanics. These techniques are used to simulate the behavior of molecules from the physicochemical principles.

Polyprotein:

In protein engineering, artificial polymeric protein formed by repeats (oriented or not) of a protein or a protein domain linked by covalent (peptide, isopeptide, or disulfide) bonds. Polymerization can be achieved at the DNA (by genetic engineering techniques: in vivo) or protein (by using biochemical techniques: in vitro) level.

Proteasomes:

Large bionanomachines that degrade damaged or unneeded proteins by proteolysis (a chemical reaction that breaks peptide bonds). They are present in all kinds of cells, belonging to the class of enzymes called proteases, and they use ATP as a source of chemical energy.

Protein:

Natural biopolymer composed of up to 20 different monomers, amino acids, linked by so-called peptide bonds (a planar covalent bond), which typically acquires a unique 3D (fold) structure. The sequence of amino acids of a polypeptide is its primary structure. Proteins with quaternary structure are formed by several polypeptides, which are linked by noncovalent bonds, other covalent bonds, or both.

Protein engineering:

Discipline at the crossroads of molecular biology (includes genetic engineering, a technology to manipulate DNA), biochemistry, structural biology, and bioinformatics that aims to either the modification of proteins to improve or study its properties (redesign) or to design new proteins de novo. Usually, it involves making changes in the sequence of a gene coding for a protein (usually by polymerase chain reaction and directed mutagenesis) in order to bring about desirable changes in its structure and/or function.

Protein fold:

Unique 3D structure of proteins (also called superior structure or protein conformation) achieved by either self-assembly alone or with the help of specific proteins (molecular chaperons), which is necessary for its biological function. There are several structural levels of protein conformation: secondary (the main models are α-helix and β-sheet; the latter formed by β-strands), tertiary (final fold of a polypeptide, e.g., β-sandwich β-barrel), quaternary (resulting from the association of several polypeptides usually by noncovalent bonds). Protein structures (folds) resolved at atomic resolution are unique having an ascribed file specifying their atomic coordinates (i.e., Protein Data Bank, PDB file) and are classified somewhat artificially into discrete classes (e.g., immunoglobulin fold).

Protein folding:

Process by which a polypeptide acquires its native 3D structure (fold).

Protein nanomechanics:

New discipline in charge of measuring forces, distances, motions, energies, and deformations involved in the manipulation of individual proteins or protein complexes, which are typically in the submicrometer and subnanonewton ranges.

Protein unfolding:

Process by which a native protein loses its native folding becoming “denatured.”

Single-molecule force spectroscopy (SMFS):

Technique carried out by several instruments (AFM, optical tweezers, or biomembrane force probe) consisting in stretching single molecules to measure the resistance forces (length-clamp mode) or distances traveled between resistance barriers (force-clamp mode).

Unfolding (folding) pathway:

Energetic representation of the pathway of an unfolding (folding) reaction.

Bibliography

Primary Literature

  • Abe H, Go N (1981) Noninteracting local-structure model of folding and unfolding transition in globular proteins, II, Application to two-dimensional lattice proteins. Biopolymers 20:1013–1031

    Google Scholar 

  • Abu-Lail NI, Ohashi T, Clark RL, Erickson HP, Zauscher S (2005) Understanding the elasticity of fibronectin fibrils: unfolding strengths of FN-III and GFP domains measured by single-molecule force spectroscopy. Matrix Biol 25:175–184

    Google Scholar 

  • Ainavarapu SR, Li L, Badilla CL, Fernandez JM (2005) Ligand binding modulates the mechanical stability of dihydrofolate reductase. Biophys J 89:3337–3344

    Google Scholar 

  • Ainavarapu SR, Brujic J, Huang HH, Wiita AP, Lu H, Li L, Walther KA, Carrion-Vazquez M, Li H, Fernandez JM (2007) Contour length and refolding rate of a small protein controlled by engineered disulfide bonds. Biophys J 92:225–233

    Google Scholar 

  • Alberts B (1998) The cell as a collection of protein machines: preparing the next generation of molecular biologists. Cell 92:291–294

    Google Scholar 

  • Bao G, Suresh S (2003) Cell and molecular mechanics of biological materials. Nat Mater 2:715–725

    ADS  Google Scholar 

  • Batey S, Randles LG, Steward A, Clarke J (2005) Cooperative folding in a multi-domain protein. J Mol Biol 349:1045–1059

    Google Scholar 

  • Bechtluft P, van Leeuwen RG, Tyreman M, Tomkiewicz D, Nouwen N, Tepper HL, Driessen AJ, Tans SJ (2007) Direct observation of chaperone-induced changes in a protein folding pathway. Science 318:1458–1461

    ADS  Google Scholar 

  • Bell GI (1978) Models for the specific adhesion of cells to cells. Science 200:618–627

    ADS  Google Scholar 

  • Best RB, Li B, Steward A, Daggett V, Clarke J (2001) Can non-mechanical proteins withstand force? Stretching barnase by atomic force microscopy and molecular dynamics simulation. Biophys J 81:2344–2356

    Google Scholar 

  • Best RB, Fowler SB, Toca-Herrera JL, Clarke J (2002) A simple method for proving the mechanical unfolding pathway of proteins in detail. Proc Natl Acad Sci U S A 99:12143–12148

    ADS  Google Scholar 

  • Best RB, Brockwell DJ, Toca-Herrera JL, Blake AW, Smith DA, Radford SE, Clarke J (2003a) Force mode atomic force microscopy as a tool for protein folding studies. Anal Chim Acta 479:87–105

    Google Scholar 

  • Best RB, Fowler SB, Toca-Herrera JL, Steward A, Paci E, Clarke J (2003b) Mechanical unfolding of a titin Ig domain: structure of transition state revealed by combining atomic force microscopy, protein engineering and molecular dynamics simulations. J Mol Biol 330:867–877

    Google Scholar 

  • Bhasin N, Carl P, Harper S, Feng G, Lu H, Speicher DW, Discher DE (2004) Chemistry on a single protein, vascular cell adhesion molecule-1, during forced unfolding. J Biol Chem 279:45865–45874

    Google Scholar 

  • Binnig G, Quate CF, Gerber C (1986) Atomic force microscope. Phys Rev Lett 56:930–933

    ADS  Google Scholar 

  • Brockwell DJ, Beddard GS, Clarkson J, Zinober RC, Blake AW, Trinick J, Olmsted PD, Smith DA, Radford SE (2002) The effect of core destabilization on the mechanical resistance of I27. Biophys J 83:458–472

    Google Scholar 

  • Brockwell DJ, Paci E, Zinober RC, Beddard GS, Olmsted PD, Smith DA, Perham RN, Radford SE (2003) Pulling geometry defines the mechanical resistance of a beta-sheet protein. Nat Struct Biol 10:731–737

    Google Scholar 

  • Bullard B, Garcia T, Benes V, Leake MC, Linke WA, Oberhauser AF (2006) The molecular elasticity of the insect flight muscle proteins projectin and kettin. Proc Natl Acad Sci U S A 103:4451–4456

    ADS  Google Scholar 

  • Bustamante C, Macosko JC, Wuite GJ (2000) Grabbing the cat by the tail: manipulating molecules one by one. Nat Rev Mol Cell Biol 1:130–136

    Google Scholar 

  • Bustamante C, Chemla YR, Forde NR, Izhaky D (2004) Mechanical processes in biochemistry. Annu Rev Biochem 73:705–748

    Google Scholar 

  • Cao Y, Li H (2007) Polyprotein of GB1 is an ideal artificial elastomeric protein. Nat Mater 6:109–114

    MathSciNet  ADS  Google Scholar 

  • Carl P, Kwok CH, Manderson G, Speicher DW, Discher DE (2001) Forced unfolding modulated by disulfide bonds in the Ig domains of a cell adhesion molecule. Proc Natl Acad Sci U S A 98:1565–1570

    ADS  Google Scholar 

  • Carrion-Vazquez M, Marszalek PE, Oberhauser AF, Fernandez JM (1999a) Atomic force microscopy captures length phenotypes in single proteins. Proc Natl Acad Sci U S A 96:11288–11292

    ADS  Google Scholar 

  • Carrion-Vazquez M, Oberhauser AF, Fowler SB, Marszalek PE, Broedel SE, Clarke J, Fernandez JM (1999b) Mechanical and chemical unfolding of a single protein: a comparison. Proc Natl Acad Sci U S A 96:3694–3699

    ADS  Google Scholar 

  • Carrion-Vazquez M, Oberhauser AF, Fisher TE, Marszalek PE, Li H, Fernandez JM (2000) Mechanical design of proteins studied by single-molecule force spectroscopy and protein engineering. Prog Biophys Mol Biol 74:63–91

    Google Scholar 

  • Carrion-Vazquez M, Li H, Lu H, Marszalek PE, Oberhauser AF, Fernandez JM (2003) The mechanical stability of ubiquitin is linkage dependent. Nat Struct Biol 10:738–743

    Google Scholar 

  • Carrión-Vázquez M, Oberhauser AF, Díez H, Hervás R, Oroz J, Fernández J, Martínez-Martín D (2006) Protein nanomechanics, as studied by AFM single-molecule force spectroscopy. In: Arrondo JLR, Alonso A (eds) Advanced techniques in biophysics. Springer, Berlin, pp 163–245

    Google Scholar 

  • Cecconi C, Shank EA, Bustamante C, Marqusee S (2005) Direct observation of the three-state folding of a single protein molecule. Science 309:2057–2060

    ADS  Google Scholar 

  • Cieplak M (2005) Mechanical stretching of proteins: calmodulin and titin. Phys A 352:28–42

    Google Scholar 

  • Cieplak M, Szymczak P (2006) Protein folding in a force clamp. J Chem Phys 124:194901

    ADS  Google Scholar 

  • Cieplak M, Hoang TX, Robbins MO (2002) Folding and stretching in a Go-like model of titin. Proteins 49:114–124

    Google Scholar 

  • Cieplak M, Hoang TX, Robbins MO (2004) Thermal effects in stretching of Go-like models of titin and secondary structures. Proteins 56:285–297

    Google Scholar 

  • Cieplak M, Filipek S, Janovjak H, Krzysko KA (2006) Pulling single bacteriorhodopsin out of a membrane: comparison of simulation and experiment. Biochim Biophys Acta 1758:537–544

    Google Scholar 

  • Clausen-Schaumann H, Seitz M, Krautbauer R, Gaub HE (2000) Force spectroscopy with single bio-molecules. Curr Opin Chem Biol 4:524–530

    Google Scholar 

  • Clementi C, Nymeyer H, Onuchic JN (2000) Topological and energetic factors: what determines the structural details of the transition state ensemble and “en-route” intermediates for protein folding? An investigation for small globular proteins. J Mol Biol 298:937–953

    Google Scholar 

  • Collin D, Ritort F, Jarzynski C, Smith SB, Tinoco I Jr, Bustamante C (2005) Verification of the Crooks fluctuation theorem and recovery of RNA folding free energies. Nature 437:231–234

    ADS  Google Scholar 

  • Dietz H, Rief M (2004) Exploring the energy landscape of GFP by single-molecule mechanical experiments. Proc Natl Acad Sci U S A 101:16192–16197

    ADS  Google Scholar 

  • Dietz H, Rief M (2006) Protein structure by mechanical triangulation. Proc Natl Acad Sci U S A 103:1244–1247

    ADS  Google Scholar 

  • Dietz H, Berkemeier F, Bertz M, Rief M (2006) Anisotropic deformation response of single protein molecules. Proc Natl Acad Sci U S A 103:12724–12728

    ADS  Google Scholar 

  • Evans E, Ritchie K (1997) Dynamic strength of molecular adhesion bonds. Biophys J 72:1541–1555

    Google Scholar 

  • Evans E, Ritchie K, Merkel R (1995) Sensitive force technique to probe molecular adhesion and structural linkages at biological interfaces. Biophys J 68:2580–2587

    Google Scholar 

  • Fernandez JM, Li H (2004) Force-clamp spectroscopy monitors the folding trajectory of a single protein. Science 303:1674–1678

    ADS  Google Scholar 

  • Fersht AR, Matouschek A, Serrano L (1992) The folding of an enzyme. I. Theory of protein engineering analysis of stability and pathway of protein folding. J Mol Biol 224:771–782

    Google Scholar 

  • Forman JR, Clarke J (2007) Mechanical unfolding of proteins: insights into biology, structure and folding. Curr Opin Struct Biol 17:58–66

    Google Scholar 

  • Fowler SB, Best RB, Toca-Herrera JL, Rutherford TJ, Steward A, Paci E, Karplus M, Clarke J (2002) Mechanical unfolding of a titin Ig domain: structure of unfolding intermediate revealed by combining AFM, molecular dynamics simulations, NMR and protein engineering. J Mol Biol 322:841–849

    Google Scholar 

  • Gao M, Sotomayor M, Villa E, Lee EH, Schulten K (2006) Molecular mechanisms of cellular mechanics. Phys Chem Chem Phys 8:3692–3706

    Google Scholar 

  • Garcia-Manyes S, Brujic J, Badilla CL, Fernandez JM (2007) Force-clamp spectroscopy of single-protein monomers reveals the individual unfolding and folding pathways of I27 and ubiquitin. Biophys J 93:2436–2446

    Google Scholar 

  • Geiger B, Bershadsky A (2002) Exploring the neighborhood: adhesion-coupled cell mechanosensors. Cell 110:139–142

    Google Scholar 

  • Giannone G, Sheetz MP (2006) Substrate rigidity and force define form through tyrosine phosphatase and kinase pathways. Trends Cell Biol 16:213–223

    Google Scholar 

  • Grubmuller H, Heymann B, Tavan P (1996) Ligand binding: molecular mechanics calculation of the streptavidin biotin rupture force. Science 271:997–999

    ADS  Google Scholar 

  • Hinterdorfer P (2002) Molecular recognition studies using the atomic force microscope. Methods Cell Biol 68:115–139

    Google Scholar 

  • Hoang TX, Cieplak M (2000) Molecular dynamics of folding of secondary structures in Go-like models of proteins. J Chem Phys 112:6851–6862

    ADS  Google Scholar 

  • Howard J (2001) Mechanics of motor proteins and the cytoskeleton. Sinauer Associates, Sunderland

    Google Scholar 

  • Huang L, Kirmizialtin S, Makarov DE (2005) Computer simulations of the translocation and unfolding of a protein pulled mechanically through a pore. J Chem Phys 123:124903

    ADS  Google Scholar 

  • Huxley H, Hanson J (1954) Changes in the cross-striations of muscle during contraction and stretch and their structural interpretation. Nature 173:973–976

    ADS  Google Scholar 

  • Hyeon CB, Thirumalai D (2003) Can energy landscape roughness of proteins and RNA be measured by using mechanical unfolding experiments? Proc Natl Acad Sci U S A 100:10249–10253

    ADS  Google Scholar 

  • Johnson CP, Tang HY, Carag C, Speicher DW, Discher DE (2007) Forced unfolding of proteins within cells. Science 317:663–666

    ADS  Google Scholar 

  • Junker JP, Hell K, Schlierf M, Neupert W, Rief M (2005) Influence of substrate binding on the mechanical stability of mouse dihydrofolate reductase. Biophys J 89:L46–L48

    Google Scholar 

  • Karanicolas J, Brooks CL III (2002) The origins of asymmetry in the folding transition states of protein L and protein G. Protein Sci 11:2351–2361

    Google Scholar 

  • Kedrov A, Janovjak H, Sapra KT, Müller DJ (2007) Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy. Annu Rev Biophys Biomol Struct 36:233–260

    Google Scholar 

  • Kellermayer MS (2005) Visualizing and manipulating individual protein molecules. Physiol Meas 26:R119–R153

    ADS  Google Scholar 

  • Kellermayer MS, Smith SB, Granzier HL, Bustamante C (1997) Folding-unfolding transitions in single titin molecules characterized with laser tweezers. Science 276:1112–1116

    Google Scholar 

  • Klimov DK, Thirumalai D (2000) Native topology determines force-induced unfolding pathways in globular proteins. Proc Natl Acad Sci U S A 97:7254–7259

    ADS  Google Scholar 

  • Law R, Carl P, Harper S, Dalhaimer P, Speicher DW, Discher DE (2003) Cooperativity in forced unfolding of tandem spectrin repeats. Biophys J 84:533–544

    Google Scholar 

  • Leake MC, Grutzner A, Kruger M, Linke WA (2006) Mechanical properties of cardiac titin’s N2B-region by single-molecule atomic force spectroscopy. J Struct Biol 155:263–272

    Google Scholar 

  • Lee G, Abdi K, Jiang Y, Michaely P, Bennett V, Marszalek PE (2006) Nanospring behaviour of ankyrin repeats. Nature 440:246–249

    ADS  Google Scholar 

  • Lee C-K, Wang Y-M, Huang L-S, Lin S (2007) Atomic force microscopy: determination of unbinding force, off rate and energy barrier for protein-ligand interaction. Micron 38:446–461

    Google Scholar 

  • Li H, Oberhauser AF, Fowler SB, Clarke J, Fernandez JM (2000a) Atomic force microscopy reveals the mechanical design of a modular protein. Proc Natl Acad Sci U S A 97:6527–6531

    ADS  Google Scholar 

  • Li H, Carrion-Vazquez M, Oberhauser AF, Marszalek PE, Fernandez JM (2000b) Point mutations alter the mechanical stability of immunoglobulin modules. Nat Struct Biol 7:1117–1120

    Google Scholar 

  • Li H, Oberhauser AF, Redick SD, Carrion-Vazquez M, Erickson HP, Fernandez JM (2001) Multiple conformations of PEVK proteins detected by single-molecule techniques. Proc Natl Acad Sci U S A 98:10682–10686

    ADS  Google Scholar 

  • Li H, Linke WA, Oberhauser AF, Carrion-Vazquez M, Kerkvliet JG, Lu H, Marszalek PE, Fernandez JM (2002) Reverse engineering of the giant muscle protein titin. Nature 418:998–1002

    ADS  Google Scholar 

  • Liphardt J, Dumont S, Smith SB, Tinoco I Jr, Bustamante C (2002) Equilibrium information from nonequilibrium measurements in an experimental test of Jarzynski’s equality. Science 296:1832–1853

    ADS  Google Scholar 

  • Lu H, Isralewitz B, Krammer A, Vogel V, Schulten K (1998) Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation. Biophys J 75:662–671

    Google Scholar 

  • Makarov DE, Hansma PK, Metiu H (2001) Kinetic Monte Carlo simulation of titin unfolding. J Chem Phys 114:9663–9673

    ADS  Google Scholar 

  • Marszalek PE, Lu H, Li H, Carrion-Vazquez M, Oberhauser AF, Schulten K, Fernandez JM (1999) Mechanical unfolding intermediates in titin modules. Nature 402:100–103

    ADS  Google Scholar 

  • Maruyama K, Kimura S, Ohashi K, Kuwano Y (1981) Connectin, an elastic protein of muscle. Identification of “titin” with connectin. J Biochem 89:701–709

    Google Scholar 

  • Matouschek A (2003) Protein unfolding-an important process in vivo? Curr Opin Struct Biol 13:98–109

    Google Scholar 

  • Maxwell KL, Wildes D, Zarrine-Afsar A, de los Rios MA, Brown AG et al (2005) Protein folding: defining a “standard” set of experimental conditions and a preliminary kinetic data set of two-state proteins. Protein Sci 14:602–616

    Google Scholar 

  • Mehta AD, Rief M, Spudich JA (1999) Biomechanics, one molecule at a time. J Biol Chem 274:14517–14520

    Google Scholar 

  • Merkel R (2001) Force spectroscopy on single passive biomolecules and single biomolecular bonds. Phys Rep 346:344–385

    ADS  Google Scholar 

  • Miller E, Garcia T, Hultgren S, Oberhauser AF (2006) The mechanical properties of E. coli type 1 pili measured by atomic force microscopy techniques. Biophys J 91:3848–3856

    Google Scholar 

  • Müller DJ, Engel A (2007) Atomic force microscopy and spectroscopy of native membrane proteins. Nat Protoc 2:2191–2197

    Google Scholar 

  • Neher E, Sakmann B (1976) Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260:799–802

    ADS  Google Scholar 

  • Neuman KC, Lionnet T, Allemand J-F (2007) Single-molecule micromanipulation techniques. Annu Rev Mater Res 37:33–67

    ADS  Google Scholar 

  • Ng SP, Rounsevell RWS, Steward A, Geierhaas CD, Williams PM, Paci E, Clarke J (2005) Mechanical unfolding of TNfn3: the unfolding pathway of a fnIII domain probed by protein engineering, AFM and MD simulation. J Mol Biol 350:776–789

    Google Scholar 

  • Oberhauser AF, Carrión-Vázquez M (2008) Mechanical biochemistry of proteins one molecule at a time. J Biol Chem 283:6617–6621

    Google Scholar 

  • Oberhauser AF, Marszalek PE, Erickson HP, Fernandez JM (1998) The molecular elasticity of tenascin, an extracellular matrix protein. Nature 393:181–185

    ADS  Google Scholar 

  • Oberhauser AF, Marszalek PE, Carrion-Vazquez M, Fernandez JM (1999) Single protein misfolding events captured by atomic force microscopy. Nat Struct Biol 6:1025–1028

    Google Scholar 

  • Oberhauser AF, Badilla-Fernandez C, Carrion-Vazquez M, Fernandez JM (2002) The mechanical hierarchies of fibronectin observed with single-molecule AFM. J Mol Biol 319:433–447

    Google Scholar 

  • Perez-Jimenez R, Garcia-Manyes S, Ainavarapu SR, Fernandez JM (2006) Mechanical unfolding pathways of the enhanced yellow fluorescent protein revealed by single molecule force spectroscopy. J Biol Chem 281:40010–40014

    Google Scholar 

  • Prakash S, Matouschek A (2004) Protein unfolding in the cell. Trends Biochem Sci 29:593–600

    Google Scholar 

  • Qian F, Wei W, Germino G, Oberhauser A (2005) The nanomechanics of polycystin-1 extracellular region. J Biol Chem 280:40723–40730

    Google Scholar 

  • Rief M, Grubmuller H (2002) Force spectroscopy of single biomolecules. Chemphyschem 3:255–261

    Google Scholar 

  • Rief M, Gautel M, Oesterhelt F, Fernandez JM, Gaub HE (1997) Reversible unfolding of individual titin immunoglobulin domains by AFM. Science 276:1109–1112

    Google Scholar 

  • Rief M, Pascual J, Saraste M, Gaub HE (1999) Single molecule force spectroscopy of spectrin repeats: low unfolding forces in helix bundles. J Mol Biol 286:553–561

    Google Scholar 

  • Ritort F (2006) Single-molecule experiments in biological physics: methods and applications. J Phys Condens Matter 18:R531–R583

    ADS  Google Scholar 

  • Rounsevell R, Forman JR, Clarke J (2004) Atomic force microscopy: mechanical unfolding of proteins. Methods 34:100–111

    Google Scholar 

  • Samorì B, Zuccheri G, Baschieri R (2005) Protein unfolding and refolding under force: methodologies for nanomechanics. Chemphyschem 6:29–34

    Google Scholar 

  • Sarkar A, Robertson RB, Fernandez JM (2004) Simultaneous atomic force microscope and fluorescence measurements of protein unfolding using a calibrated evanescent wave. Proc Natl Acad Sci U S A 101:12882–12886

    ADS  Google Scholar 

  • Sarkar A, Caamano S, Fernandez JM (2005) The elasticity of individual titin PEVK exons measured by single molecule atomic force microscopy. J Biol Chem 280:6261–6264

    Google Scholar 

  • Sato T, Esaki M, Fernandez JM, Endo T (2005) Comparison of the protein-unfolding pathways between mitochondrial protein import and atomic-force microscopy measurements. Proc Natl Acad Sci U S A 102:17999–18004

    ADS  Google Scholar 

  • Sauer RT, Bolon DN, Burton BM, Burton RE, Flynn JM, Grant RA, Hersch GL, Joshi SA, Kenniston JA, Levchenko I, Neher SB, Oakes E, Siddiqui SM, Wah DA, Baker TA (2004) Sculpting the proteome with AAA(+) proteases and disassembly machines. Cell 119:9–18

    Google Scholar 

  • Schlierf M, Li H, Fernandez JM (2004) The unfolding kinetics of ubiquitin captured with single-molecule force-clamp techniques. Proc Natl Acad Sci U S A 101:7299–7304

    ADS  Google Scholar 

  • Schwaiger I, Sattler C, Hostetter DR, Rief M (2002) The myosin coiled-coil is a truly elastic protein structure. Nat Mater 1:232–235

    ADS  Google Scholar 

  • Schwaiger I, Schleicher M, Noegel AA, Rief M (2005) The folding pathway of a fast-folding immunoglobulin domain revealed by single-molecule mechanical experiments. EMBO Rep 6:1–6

    Google Scholar 

  • Sharma D, Perisic O, Peng Q, Cao Y, Lam C, Lu H, Li H (2007) Single-molecule force spectroscopy reveals a mechanically stable protein fold and the rational tuning of its mechanical stability. Proc Natl Acad Sci U S A 104:9278–9283

    ADS  Google Scholar 

  • Shtilerman M, Lorimer GH, Englander SW (1999) Chaperonin function: folding by forced unfolding. Science 284:822–825

    ADS  Google Scholar 

  • Smith ML, Gourdon D, Little WC, Kubow KE, Eguiluz RA, Luna-Morris S, Vogel V (2007) Force-induced unfolding of fibronectin in the extracellular matrix of living cells. PLoS Biol 5:e268

    Google Scholar 

  • Sotomayor M, Schulten K (2007) Single-molecule experiments in vitro and in silico. Science 316:1144–1148

    ADS  Google Scholar 

  • Sulkowska JI, Cieplak M (2007) Mechanical stretching of proteins – a theoretical survey of the Protein Data Bank – a topical review. J Phys Condens Matter 19:283201

    ADS  Google Scholar 

  • Sulkowska JI, Cieplak M (2008a) Stretching to understand proteins-A survey of the Protein Data Bank. Biophys J 94:6–13

    Google Scholar 

  • Sulkowska JI, Cieplak M (2008b) Selection of optimal variants of Go-like models of protein through studies of stretching. Biophys J 95:3174–3191

    Google Scholar 

  • Sulkowska JI, Sulkowski P, Szymczak P, Cieplak M (2008) Tightening of knots in proteins. Phys Rev Lett 100:058106

    ADS  Google Scholar 

  • Takada S (1999) Go-ing for the prediction of protein folding mechanisms. Proc Natl Acad Sci U S A 96:11609–11700

    Google Scholar 

  • Tian P, Andricioaei I (2005) Repetitive pulling catalyzes co-translocational unfolding of barnase during import through a mitochondrial pore. J Mol Biol 350:1017–1034

    Google Scholar 

  • Trylska J, Tozzini V, McCammon JA (2005) Exploring global motions and correlations in the ribosome. Biophys J 89:1455–1463

    Google Scholar 

  • Tskhovrebova L, Trinick J (2003) Titin: properties and family relationships. Nat Rev Mol Cell Biol 4:679–789

    Google Scholar 

  • Urry DW, Hugel T, Seitz M, Gaub HE, Sheiba L, Dea J, Xu J, Parker T (2002) Elastin: a representative ideal protein elastomer. Philos Trans R Soc Lond B Biol Sci 357:169–184

    Google Scholar 

  • Valbuena A, Oroz J, Vera AM, Gimeno A, Gómez-Herrero J, Carrión-Vázquez M (2007) Quasi-simultaneous imaging/pulling analysis of polyprotein molecules by AFM. Rev Sci Instrum 78:113707

    ADS  Google Scholar 

  • Veitshan T, Klimov D, Thirumalai D (1997) Protein folding kinetics: timescales, pathways and energy landscapes in terms of sequence-dependent properties. Fold Des 2:1–22

    Google Scholar 

  • Vogel V (2006) Mechanotransduction involving multimodular proteins: converting force into biochemical signals. Annu Rev Biophys Biomol Struct 35:459–488

    Google Scholar 

  • Vogel V, Sheetz M (2006) Local force and geometry sensing regulate cell functions. Nat Rev Mol Cell Biol 7:265–275

    Google Scholar 

  • Walther KA, Grater F, Dougan L, Badilla CL, Berne BJ, Fernandez JM (2007) Signatures of hydrophobic collapse in extended proteins captured with force spectroscopy. Proc Natl Acad Sci U S A 104:7916–7921

    ADS  Google Scholar 

  • Wang K, McClure J, Tu A (1979) Titin: major myofibrilar components of striated muscle. Proc Natl Acad Sci U S A 76:3698–3702

    ADS  Google Scholar 

  • Weisel JW, Shuman H, Litvinov RI (2003) Protein-protein unbinding induced by force: single-molecule studies. Curr Opin Struct Biol 13:227–235

    Google Scholar 

  • West DK, Brockwell DJ, Olmsted PD, Radford SE, Paci E (2006a) Mechanical resistance of proteins explained using simple molecular models. Biophys J 90:287–297

    Google Scholar 

  • West DK, Brockwell DJ, Paci E (2006b) Prediction of the translocation kinetics of a protein from its mechanical properties. Biophys J 91:L51–L53

    Google Scholar 

  • Wiita AP, Ainavarapu SR, Huang HH, Fernandez JM (2006) Force-dependent chemical kinetics of disulfide bond reduction observed with single-molecule techniques. Proc Natl Acad Sci U S A 103:7222–7227

    ADS  Google Scholar 

  • Wiita AP, Perez-Jimenez R, Walther KA, Grater F, Berne BJ, Holmgren A, Sanchez-Ruiz JM, Fernandez JM (2007) Probing the chemistry of thioredoxin catalysis with force. Nature 450:124–127

    ADS  Google Scholar 

  • Wilcox AJ, Choy J, Bustamante C, Matouschek A (2005) Effect of protein structure on mitochondrial import. Proc Natl Acad Sci U S A 102:15435–15440

    ADS  Google Scholar 

  • Yang G, Cecconi C, Baase WA, Vetter IR, Breyer WA, Haack JA, Matthews BW, Dahlquist FW, Bustamante C (2000) Solid-state synthesis and mechanical unfolding of polymers of T4 lysozyme. Proc Natl Acad Sci U S A 97:139–144

    ADS  Google Scholar 

  • Zhuang X, Rief M (2003) Single-molecule folding. Curr Opin Struct Biol 13:88–97

    Google Scholar 

  • Zlatanova J, van Holde K (2006) Single-molecule biology: what is it and how does it work? Mol Cell 24:317–329

    Google Scholar 

  • Zlatanova J, Lindsay SM, Leuba SH (2000) Single molecule force spectroscopy in biology using the atomic force microscope. Prog Biophys Mol Biol 74:37–61

    Google Scholar 

Books and Reviews

  • Boal D (2002) Mechanics of the cell. Cambridge University Press, Cambridge

    Google Scholar 

  • Brande C, Tooze J (1999) Introduction to protein structure, 2nd edn. Garland Publishing, New York

    Google Scholar 

  • Goodsell DS (2004) Bionanotechnology: lessons from nature. Wiley, Hoboken

    Google Scholar 

  • Grosberg AY, Khokhlov AR (1997) Giant molecules: here, there and everywhere. Academic, San Diego

    Google Scholar 

  • Grubmüller H, Schulten K (eds) (2007) Advances in molecular dynamics simulations. J Struct Biol 157(Special issue):443–615

    Google Scholar 

  • Leuba SH, Zlatanova J (2000) Biology at the single-molecule level. Pergamon Press, Oxford

    Google Scholar 

  • Wainwright SA, Biggs WD, Currey JD, Gosline JM (1976) Mechanical design in organisms. Princeton University Press, Princeton

    Google Scholar 

Download references

Acknowledgments

This work was funded by grants from the Spanish Ministry of Science and Education (BIO2007-67116), the Consejería de Educación of the Madrid Community (S-0505/MAT/0283), and the Spanish Research Council (200620 F00) to M.C.-V., from the NIH (R01DK073394), the John Sealy Memorial Endowment Fund for Biomedical Research, and the Polycystic Kidney Foundation (116a2r) to A.F.O., and from the Ministry of Science and Higher Education (N N202 0852 33) to M.C. We apologize to all researchers whose pioneering work was not cited due to limitations of space.

Author information

Authors and Affiliations

  1. CSIC & CIBERNED (Network on Degenerative Diseases), Cajal Institute, Madrid, Spain

    Mariano Carrión-Vázquez

  2. Institute of Physics, Polish Academy of Sciences, Warsaw, Poland

    Marek Cieplak

  3. Department of Neuroscience and Cell Biology, Department of Biochemistry and Molecular Biology and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA

    Andrés F. Oberhauser

Authors
  1. Mariano Carrión-Vázquez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marek Cieplak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrés F. Oberhauser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mariano Carrión-Vázquez .

Editor information

Editors and Affiliations

  1. Ramtech Ltd., Larkspur, California, USA

    Robert A. Meyers

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this entry

Cite this entry

Carrión-Vázquez, M., Cieplak, M., Oberhauser, A.F. (2015). Protein Mechanics at the Single-Molecule Level. In: Meyers, R. (eds) Encyclopedia of Complexity and Systems Science. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27737-5_420-6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-27737-5_420-6

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Online ISBN: 978-3-642-27737-5

  • eBook Packages: Springer Reference Physics and AstronomyReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics

Publish with us

Policies and ethics

Search

Navigation