TY - JOUR
T1 - Molecular Basis of Passive Stress Relaxation in Human Soleus Fibers
T2 - Assessment of the Role of Immunoglobulin-like Domain Unfolding
AU - Trombitás, K.
AU - Wu, Y.
AU - McNabb, M.
AU - Greaser, M.
AU - Kellermayer, M. S.Z.
AU - Labeit, S.
AU - Granzier, Henk L.
N1 - Funding Information:
This work was supported by the National Institutes of Health (HL61497 and HL62881 to H.G.; HL62466 to M.G.), Deutsche Forschungsgemeinschaft (La668/6-2 and 7-1 to S.L.), and Hungarian Science Foundation (OTKA T037935 to M.S.Z.K.).
PY - 2003/11
Y1 - 2003/11
N2 - Titin (also known as connectin) is the main determinant of physiological levels of passive muscle force. This force is generated by the extensible I-band region of the molecule, which is constructed of the PEVK domain and tandem-immunoglobulin segments comprising serially linked immunoglobulin (Ig)-like domains. It is unresolved whether under physiological conditions Ig domains remain folded and act as "spacers" that set the sarcomere length at which the PEVK extends or whether they contribute to titin's extensibility by unfolding. Here we focused on whether Ig unfolding plays a prominent role in stress relaxation (decay of force at constant length after stretch) using mechanical and immunolabeling studies on relaxed human soleus muscle fibers and Monte Carlo simulations. Simulation experiments using Ig-domain unfolding parameters obtained in earlier single-molecule atomic force microscopy experiments recover the phenomenology of stress relaxation and predict large-scale unfolding in titin during an extended period (>∼20 min) of relaxation. By contrast, immunolabeling experiments failed to demonstrate large-scale unfolding. Thus, under physiological conditions in relaxed human soleus fibers, Ig domains are more stable than predicted by atomic force microscopy experiments. Ig-domain unfolding did not become more pronounced after gelsolin treatment, suggesting that the thin filament is unlikely to significantly contribute to the mechanical stability of the domains. We conclude that in human soleus fibers, Ig unfolding cannot solely explain stress relaxation.
AB - Titin (also known as connectin) is the main determinant of physiological levels of passive muscle force. This force is generated by the extensible I-band region of the molecule, which is constructed of the PEVK domain and tandem-immunoglobulin segments comprising serially linked immunoglobulin (Ig)-like domains. It is unresolved whether under physiological conditions Ig domains remain folded and act as "spacers" that set the sarcomere length at which the PEVK extends or whether they contribute to titin's extensibility by unfolding. Here we focused on whether Ig unfolding plays a prominent role in stress relaxation (decay of force at constant length after stretch) using mechanical and immunolabeling studies on relaxed human soleus muscle fibers and Monte Carlo simulations. Simulation experiments using Ig-domain unfolding parameters obtained in earlier single-molecule atomic force microscopy experiments recover the phenomenology of stress relaxation and predict large-scale unfolding in titin during an extended period (>∼20 min) of relaxation. By contrast, immunolabeling experiments failed to demonstrate large-scale unfolding. Thus, under physiological conditions in relaxed human soleus fibers, Ig domains are more stable than predicted by atomic force microscopy experiments. Ig-domain unfolding did not become more pronounced after gelsolin treatment, suggesting that the thin filament is unlikely to significantly contribute to the mechanical stability of the domains. We conclude that in human soleus fibers, Ig unfolding cannot solely explain stress relaxation.
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U2 - 10.1016/S0006-3495(03)74732-8
DO - 10.1016/S0006-3495(03)74732-8
M3 - Article
C2 - 14581214
AN - SCOPUS:0242322488
SN - 0006-3495
VL - 85
SP - 3142
EP - 3153
JO - Biophysical Journal
JF - Biophysical Journal
IS - 5
ER -