Mechanical fatigue in repetitively stretched single molecules of titin

Miklós S Z Kellermayer, Steven B. Smith, Carlos Bustamante, Hendrikus "Henk" Granzier

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Relaxed striated muscle cells exhibit mechanical fatigue when exposed to repeated stretch and release cycles. To understand the molecular basis of such mechanical fatigue, single molecules of the giant filamentous protein titin, which is the main determinant of sarcomeric elasticity, were repetitively stretched and released while their force response was characterized with optical tweezers. During repeated stretch-release cycles titin becomes mechanically worn out in a process we call molecular fatigue. The process is characterized by a progressive shift of the stretch-force curve toward increasing end-to-end lengths, indicating that repeated mechanical cycles increase titin's effective contour length. Molecular fatigue occurs only in a restricted force range (0-25 pN) during the initial part of the stretch half-cycle, whereas the rest of the force response is repeated from one mechanical cycle to the other. Protein-folding models fail to explain molecular fatigue on the basis of an incomplete refolding of titin's globular domains. Rather, the process apparently derives from the formation of labile nonspecific bonds cross-linking various sites along a pre-unfolded titin segment. Because titin's molecular fatigue occurs in a physiologically relevant force range, the process may play an important role in dynamically adjusting muscle's response to the recent history of mechanical perturbations.

Original languageEnglish (US)
Pages (from-to)852-863
Number of pages12
JournalBiophysical Journal
Volume80
Issue number2
StatePublished - 2001
Externally publishedYes

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Connectin
Fatigue
Optical Tweezers
Striated Muscle
Protein Folding
Elasticity
Muscle Cells
History
Muscles

ASJC Scopus subject areas

  • Biophysics

Cite this

Kellermayer, M. S. Z., Smith, S. B., Bustamante, C., & Granzier, H. H. (2001). Mechanical fatigue in repetitively stretched single molecules of titin. Biophysical Journal, 80(2), 852-863.

Mechanical fatigue in repetitively stretched single molecules of titin. / Kellermayer, Miklós S Z; Smith, Steven B.; Bustamante, Carlos; Granzier, Hendrikus "Henk".

In: Biophysical Journal, Vol. 80, No. 2, 2001, p. 852-863.

Research output: Contribution to journalArticle

Kellermayer, MSZ, Smith, SB, Bustamante, C & Granzier, HH 2001, 'Mechanical fatigue in repetitively stretched single molecules of titin', Biophysical Journal, vol. 80, no. 2, pp. 852-863.
Kellermayer, Miklós S Z ; Smith, Steven B. ; Bustamante, Carlos ; Granzier, Hendrikus "Henk". / Mechanical fatigue in repetitively stretched single molecules of titin. In: Biophysical Journal. 2001 ; Vol. 80, No. 2. pp. 852-863.
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