Mechanical design of proteins studied by single-molecule force spectroscopy and protein engineering

Mariano Carrion-Vazquez, Andres F. Oberhauser, Thomas E. Fisher, Piotr E. Marszalek, Hongbin Li, Julio M. Fernandez

Research output: Contribution to journalReview articlepeer-review

380 Scopus citations


Mechanical unfolding and refolding may regulate the molecular elasticity of modular proteins with mechanical functions. The development of the atomic force microscopy (AFM) has recently enabled the dynamic measurement of these processes at the single-molecule level. Protein engineering techniques allow the construction of homomeric polyproteins for the precise analysis of the mechanical unfolding of single domains. α-Helical domains are mechanically compliant, whereas β-sandwich domains, particularly those that resist unfolding with backbone hydrogen bonds between strands perpendicular to the applied force, are more stable and appear frequently in proteins subject to mechanical forces. The mechanical stability of a domain seems to be determined by its hydrogen bonding pattern and is correlated with its kinetic stability rather than its thermodynamic stability. Force spectroscopy using AFM promises to elucidate the dynamic mechanical properties of a wide variety of proteins at the single molecule level and provide an important complement to other structural and dynamic techniques (e.g., X-ray crystallography, NMR spectroscopy, patch-clamp).

Original languageEnglish (US)
Pages (from-to)63-91
Number of pages29
JournalProgress in Biophysics and Molecular Biology
Issue number1-2
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Molecular Biology


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