Is Titin an Exponential Spring in Active Muscle?

Northern Arizona University, Flagstaff AZ

Investigators

Abstract

During the past century, physiologists have made remarkable progress in elucidating the molecular mechanisms of muscle contraction. Despite this progress, the goal of predicting how muscle force changes during natural movements has remained elusive. This project will advance the understanding of muscle contraction by (1) testing the hypothesis that the length and stiffness of the giant, elastic titin protein changes when calcium is released from the sarcoplasmic reticulum upon muscle activation and (2) developing a computer model of muscle based on this hypothesis. A mutant mouse that carries a deletion in the titin gene will be used to test the hypothesis. This research will involve: (1) gel electrophoresis to estimate molecular weights of titin in mutant genotypes, (2) force-lever experiments to characterize activation-dependent elastic properties of titin in myofibrils, single fibers and whole muscles, (3) development of a muscle model that incorporates calcium activation of titin, and (4) behavioral studies to compare kinematics and energetics of locomotion across mutant genotypes. The broader impacts of this work include: (1) interdisciplinary training of undergraduate, graduate, and post-doctoral scholars in neuroscience, engineering, and computer science, (2) participation of under-represented students, and (3) public outreach including participation in the research project by local High School teachers and students from a public science and technology magnet school. Results will be disseminated through publication in diverse media and participation in interdisciplinary conferences in the areas of computer science, engineering, and biology. This research has the potential to transform our understanding of the process of muscle activation, improve neuro-musculoskeletal simulations, inform causes and potential cures for neuromuscular diseases, and inspire the design of actuators and prostheses that function more like animal muscles.