Direction Matters: Monovalent Streptavidin/Biotin Complex under Load

Steffen M. Sedlak, Leonard C. Schendel, Marcelo C.R. Melo, Diana A. Pippig, Zaida Luthey-Schulten, Hermann E. Gaub, Rafael C. Bernardi

Research output: Contribution to journalArticle

Abstract

Novel site-specific attachment strategies combined with improvements of computational resources enable new insights into the mechanics of the monovalent biotin/streptavidin complex under load and forced us to rethink the diversity of rupture forces reported in the literature. We discovered that the mechanical stability of this complex depends strongly on the geometry in which force is applied. By atomic force microscopy-based single molecule force spectroscopy we found unbinding of biotin to occur beyond 400 pN at force loading rates of 10 nN/s when monovalent streptavidin was tethered at its C-terminus. This value is about twice as high than that for N-terminal attachment. Steered molecular dynamics simulations provided a detailed picture of the mechanics of the unbinding process in the corresponding force loading geometries. Using machine learning techniques, we connected findings from hundreds of simulations to the experimental results, identifying different force propagation pathways. Interestingly, we observed that depending on force loading geometry, partial unfolding of N-terminal region of monovalent streptavidin occurs before biotin is released from the binding pocket.

Original languageEnglish (US)
Pages (from-to)3415-3421
Number of pages7
JournalNano letters
Volume19
Issue number6
DOIs
StatePublished - Jun 12 2019

Fingerprint

biotin
Streptavidin
Biotin
Geometry
Mechanics
Mechanical stability
attachment
geometry
Learning systems
Molecular dynamics
Atomic force microscopy
loading rate
machine learning
Spectroscopy
Molecules
Computer simulation
resources
simulation
biotin-streptavidin complex
Direction compound

Keywords

  • Streptavidin/biotin
  • atomic force microscopy
  • machine learning
  • molecular dynamics
  • single-molecule force spectroscopy

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

Cite this

Sedlak, S. M., Schendel, L. C., Melo, M. C. R., Pippig, D. A., Luthey-Schulten, Z., Gaub, H. E., & Bernardi, R. C. (2019). Direction Matters: Monovalent Streptavidin/Biotin Complex under Load. Nano letters, 19(6), 3415-3421. https://doi.org/10.1021/acs.nanolett.8b04045

Direction Matters : Monovalent Streptavidin/Biotin Complex under Load. / Sedlak, Steffen M.; Schendel, Leonard C.; Melo, Marcelo C.R.; Pippig, Diana A.; Luthey-Schulten, Zaida; Gaub, Hermann E.; Bernardi, Rafael C.

In: Nano letters, Vol. 19, No. 6, 12.06.2019, p. 3415-3421.

Research output: Contribution to journalArticle

Sedlak, SM, Schendel, LC, Melo, MCR, Pippig, DA, Luthey-Schulten, Z, Gaub, HE & Bernardi, RC 2019, 'Direction Matters: Monovalent Streptavidin/Biotin Complex under Load', Nano letters, vol. 19, no. 6, pp. 3415-3421. https://doi.org/10.1021/acs.nanolett.8b04045
Sedlak, Steffen M. ; Schendel, Leonard C. ; Melo, Marcelo C.R. ; Pippig, Diana A. ; Luthey-Schulten, Zaida ; Gaub, Hermann E. ; Bernardi, Rafael C. / Direction Matters : Monovalent Streptavidin/Biotin Complex under Load. In: Nano letters. 2019 ; Vol. 19, No. 6. pp. 3415-3421.
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