title: Work Done by Titin Protein Folding Assists Muscle Contraction.
abstract: Current theories of muscle contraction propose that the power stroke of a myosin motor is the sole source of mechanical energy driving the sliding filaments of a contracting muscle. These models exclude titin, the largest protein in the human body, which determines the passive elasticity of muscles. Here, we show that stepwise unfolding/folding of titin immunoglobulin (Ig) domains occurs in the elastic I band region of intact myofibrils at physiological sarcomere lengths and forces of 6-8 pN. We use single-molecule techniques to demonstrate that unfolded titin Ig domains undergo a spontaneous stepwise folding contraction at forces below 10 pN, delivering up to 105 zJ of additional contractile energy, which is larger than the mechanical energy delivered by the power stroke of a myosin motor. Thus, it appears inescapable that folding of titin Ig domains is an important, but as yet unrecognized, contributor to the force generated by a contracting muscle.
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors: Jaime Andrés
authors: JA
authors: Rivas-Pardo
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA; Integated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Medical Center, New York, NY 10032, USA.
authors: Edward C
authors: EC
authors: Eckels
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors: Ionel
authors: I
authors: Popa
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors: Pallav
authors: P
authors: Kosuri
authors: Department of Cardiovascular Physiology, Ruhr University Bochum, 44780 Bochum, Germany. Electronic address: wolfgang.linke@rub.de.
authors: Wolfgang A
authors: WA
authors: Linke
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: jfernandez@columbia.edu.
authors: Julio M
authors: JM
authors: Fernández
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D064211:Connectin / Q000737:chemistry* / Q000502:physiology; D004548:Elasticity; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000502:physiology; D040542:Mechanotransduction, Cellular; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology* / Q000648:ultrastructure; D009218:Myosins / Q000737:chemistry* / Q000502:physiology; D000072417:Protein Domains; D017510:Protein Folding; D011817:Rabbits; D012518:Sarcomeres / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D064211:Connectin; D007074:Immunoglobulin G; D009218:Myosins