Mechanics and structure of titin oligomers explored with atomic force microscopy

Miklós S.Z. Kellermayer, Carlos Bustamante, Henk L. Granzier

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Titin is a giant polypeptide that spans half of the striated muscle sarcomere and generates passive force upon stretch. To explore the elastic response and structure of single molecules and oligomers of titin, we carried out molecular force spectroscopy and atomic force microscopy (AFM) on purified full-length skeletal-muscle titin. From the force data, apparent persistence lengths as long as ∼1.5 nm were obtained for the single, unfolded titin molecule. Furthermore, data suggest that titin molecules may globally associate into oligomers which mechanically behave as independent wormlike chains (WLCs). Consistent with this, AFM of surface-adsorbed titin molecules revealed the presence of oligomers. Although oligomers may form globally via head-to-head association of titin, the constituent molecules otherwise appear independent from each other along their contour. Based on the global association but local independence of titin molecules, we discuss a mechanical model of the sarcomere in which titin molecules with different contour lengths, corresponding to different isoforms, are held in a lattice. The net force response of aligned titin molecules is determined by the persistence length of the tandemly arranged, different WLC components of the individual molecules, the ratio of their overall contour lengths, and by domain unfolding events. Biased domain unfolding in mechanically selected constituent molecules may serve as a compensatory mechanism for contour- and persistence-length differences. Variation in the ratio and contour length of the component chains may provide mechanisms for the fine-tuning of the sarcomeric passive force response.

Original languageEnglish (US)
Pages (from-to)105-114
Number of pages10
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1604
Issue number2
DOIs
StatePublished - Jun 5 2003
Externally publishedYes

Keywords

  • AFM
  • Elasticity
  • Molecular force spectroscopy
  • Titin
  • Unfolding
  • Wormlike chain

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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