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Altered mechanical properties of titin immunoglobulin domain 27 in the presence of calcium

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Abstract

Titin (connectin) based passive force regulation has been an important physiological mechanism to adjust to varying muscle stretch conditions. Upon stretch, titin behaves as a spring capable of modulating its elastic response in accordance with changes in muscle biochemistry. One such mechanism has been the calcium-dependent stiffening of titin domains that renders the spring inherently more resistant to stretch. This transient titin-calcium interaction may serve a protective function in muscle, which could preclude costly unfolding of select domains when muscles elongate to great lengths. To test this idea, fluorescence spectroscopy was performed revealing a change in the microenvironment of the investigated immunoglobulin domain 27 (I27) of titin with calcium. Additionally, an atomic force microscope was used to evaluate the calcium-dependent regulation of passive force by stretching eight linked titin I27 domains until they unfolded. When stretching in the presence of calcium, the I27 homopolymer chain became stabilized, displaying three novel properties: (1) higher stretching forces were needed to unfold the domains, (2) the stiffness, measured as a persistence length (PL), increased and (3) the peak-to-peak distance between adjacent I27 domains increased. Furthermore, a peak order dependence became apparent for both force and PL, reflecting the importance of characterizing the dynamic unfolding history of a polymer with this approach. Together, this novel titin Ig-calcium interaction may serve to stabilize the I27 domain permitting titin to tune passive force within stretched muscle in a calcium-dependent manner.

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Notes

  1. The numbering scheme used is according to Labeit and Kolmerer (1995). I27 in skeletal muscle was later renamed I91 according to Bang et al. (2001) when titin was completely sequenced.

Abbreviations

WLC:

Worm-like chain

I27:

Titin immunoglobulin domain 27

AFM:

Atomic force microscope

PL:

Persistence length

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Acknowledgments

We thank Dr. Jane Clarke for providing us with the I27 plasmid. This work was funded by Alberta Innovates-Health Solutions, The Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and the Canada Research Chairs Program for Molecular and Cellular Biomechanics.

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Authors and Affiliations

  1. Human Performance Laboratory, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada

    Michael M. DuVall & Walter Herzog

  2. Biochemisty Research Group, Department of Biological Sciences, University of Calgary, Calgary, AB, Canada

    Jessica L. Gifford

  3. Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada

    Matthias Amrein

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  1. Michael M. DuVall
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  2. Jessica L. Gifford
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  3. Matthias Amrein
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  4. Walter Herzog
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Correspondence to Michael M. DuVall.

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DuVall, M.M., Gifford, J.L., Amrein, M. et al. Altered mechanical properties of titin immunoglobulin domain 27 in the presence of calcium. Eur Biophys J 42, 301–307 (2013). https://doi.org/10.1007/s00249-012-0875-8

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  • DOI: https://doi.org/10.1007/s00249-012-0875-8

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