REAL

Low-force transitions in single titin molecules reflect a memory of contractile history

Mártonfalvi, Zsolt and Bianco, Pasquale and Linari, Marco and Caremani, Marco and Nagy, Attila and Kellermayer, Miklós (2014) Low-force transitions in single titin molecules reflect a memory of contractile history. JOURNAL OF CELL SCIENCE, 127 (4). pp. 858-870. ISSN 0021-9533

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Abstract

Titin is a giant elastomeric muscle protein that has been suggested to function as a sensor of sarcomeric stress and strain, but the mechanisms by which it does so are unresolved. To gain insight into its mechanosensory function we manipulated single titin molecules with high-resolution optical tweezers. Discrete, step-wise transitions, with rates faster than canonical Ig domain unfolding occurred during stretch at forces as low as 5 pN. Multiple mechanisms and molecular regions (PEVK, proximal tandem-Ig, N2A) are likely to be involved. The pattern of transitions is sensitive to the history of contractile events. Monte-Carlo simulations of our experimental results predicted that structural transitions begin before the complete extension of the PEVK domain. High-resolution atomic force microscopy (AFM) supported this prediction. Addition of glutamate-rich PEVK domain fragments competitively inhibited the viscoelastic response in both single titin molecules and muscle fibers, indicating that PEVK domain interactions contribute significantly to sarcomere mechanics. Thus, under non-equilibrium conditions across the physiological force range, titin extends by a complex pattern of history-dependent discrete conformational transitions, which, by dynamically exposing ligand-binding sites, could set the stage for the biochemical sensing of the mechanical status of the sarcomere.

Item Type: Article
Additional Information: Martonfalvi Z; Bianco P authors contributed equally to this work.
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3020 Biophysics / biofizika
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 11 May 2018 08:45
Last Modified: 11 May 2018 08:45
URI: http://real.mtak.hu/id/eprint/79601

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