title: Altered mechanical properties of titin immunoglobulin domain 27 in the presence of calcium.
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.
authors.affiliation: Human Performance Laboratory, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada. mmduvall@ucalgary.ca
authors.forename: Michael M
authors.initials: MM
authors.lastname: DuVall
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Gifford
authors.forename: Matthias
authors.initials: M
authors.lastname: Amrein
authors.forename: Walter
authors.initials: W
authors.lastname: Herzog
mesh_terms: D001696:Biomechanical Phenomena / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D064211:Connectin / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D055595:Mechanical Phenomena; D017434:Protein Structure, Tertiary
chemical_list: D064211:Connectin; D007136:Immunoglobulins; D002118:Calcium