Single-molecule selection and recovery of structure-specific antibodies using atomic force microscopy

Luda S. Shlyakhtenko, Bin Yuan, Sharareh Emadi, Yuri L Lyubchenko, Michael R. Sierks

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Protein misfolding and aggregation are a common thread in numerous diseases including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, diabetes, and prion-related diseases. Elucidation of the role played by the various protein forms in these diseases requires reagents that can target specific protein forms. Here we present a method to isolate antibodies that bind to a specific protein form. We combined the imaging and nanomanipulation capabilities of atomic force microscopy (AFM) with the protein diversity of phage display antibody libraries to develop a technology that allows us to recover a single antibody molecule that is bound to a single protein molecular target. The target protein-antibody complex is first imaged by AFM, the AFM tip is then manipulated by nanolithography over the target antibody to recover the associated phage, and the antibody gene is recovered from the single phage particle by polymerase chain reaction.

Original languageEnglish (US)
Pages (from-to)192-197
Number of pages6
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume3
Issue number3
DOIs
Publication statusPublished - Sep 1 2007

    Fingerprint

Keywords

  • Atomic force microscopy
  • Phage display
  • Protein misfolding
  • Single molecule
  • Single-chain antibody fragment

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

Cite this