Titin-based tension in the cardiac sarcomere: Molecular origin and physiological adaptations

• Published in: Progress in biophysics and molecular biology Vol. 110; no. 2-3; pp. 204 - 217
• Main Authors: Anderson, Brian R., Granzier, Henk L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2012
• Subjects: Adaptation, Physiological; Animals; Connectin; Connectin - chemistry; Connectin - metabolism; Entropic force; Heart - physiology; Humans; Mechanical Phenomena; Mechanical signaling; Passive tension; Sarcomeres - metabolism; Signal Transduction; Passive tension; Entropic force; Connectin; Mechanical signaling
• ISSN: 0079-6107; 1873-1732
• DOI: 10.1016/j.pbiomolbio.2012.08.003

The passive stiffness of cardiac muscle plays a critical role in ventricular filling during diastole and is determined by the extracellular matrix and the sarcomeric protein titin. Titin spans from the Z-disk to the M-band of the sarcomere and also contains a large extensible region that acts as a molecular spring and develops passive force during sarcomere stretch. This extensible segment is titin's I-band region, and its force-generating mechanical properties determine titin-based passive tension. The properties of titin's I-band region can be modulated by isoform splicing and post-translational modification and are intimately linked to diastolic function. This review discusses the physical origin of titin-based passive tension, the mechanisms that alter titin stiffness, and titin's role in stress-sensing signaling pathways.