Observing structure, function and assembly of single proteins by AFM

Daniel J. Müller, Harald Janovjak, Tiina Lehto, Lars Kuerschner, Kurt Anderson

Research output: Contribution to journalReview articlepeer-review

147 Citations (Scopus)


Single molecule experiments provide insight into the individuality of biological macromolecules, their unique function, reaction pathways, trajectories and molecular interactions. The exceptional signal-to-noise ratio of the atomic force microscope allows individual proteins to be imaged under physiologically relevant conditions at a lateral resolution of 0.5-1nm and a vertical resolution of 0.1-0.2nm. Recently, it has become possible to observe single molecule events using this technique. This capability is reviewed on various water-soluble and membrane proteins. Examples of the observation of function, variability, and assembly of single proteins are discussed. Statistical analysis is important to extend conclusions derived from single molecule experiments to protein species. Such approaches allow the classification of protein conformations and movements. Recent developments of probe microscopy techniques allow simultaneous measurement of multiple signals on individual macromolecules, and greatly extend the range of experiments possible for probing biological systems at the molecular level. Biologists exploring molecular mechanisms will benefit from a burgeoning of scanning probe microscopes and of their future combination with molecular biological experiments.

Original languageEnglish
Pages (from-to)1-43
Number of pages43
JournalProgress in Biophysics and Molecular Biology
Issue number1-3
Publication statusPublished - May 2002
Externally publishedYes


  • Conformation
  • Single molecule force spectrometry
  • Single molecule imaging


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