title: Effects of cardiac Myosin binding protein-C on actin motility are explained with a drag-activation-competition model.
abstract: Although mutations in cardiac myosin binding protein-C (cMyBP-C) cause heart disease, its role in muscle contraction is not well understood. A mechanism remains elusive partly because the protein can have multiple effects, such as dual biphasic activation and inhibition observed in actin motility assays. Here we develop a mathematical model for the interaction of cMyBP-C with the contractile proteins actin and myosin and the regulatory protein tropomyosin. We use this model to show that a drag-activation-competition mechanism accurately describes actin motility measurements, while models lacking either drag or competition do not. These results suggest that complex effects can arise simply from cMyBP-C binding to actin.
authors.affiliation: Department of Mathematics, University of California at Davis, Davis, California. Electronic address: swalcott@math.ucdavis.edu.
authors.forename: Sam
authors.initials: S
authors.lastname: Walcott
authors.affiliation: Department of Mathematics, University of California at Davis, Davis, California.
authors.forename: Steffen
authors.initials: S
authors.lastname: Docken
authors.affiliation: Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona.
authors.forename: Samantha P
authors.initials: SP
authors.lastname: Harris
mesh_terms: D000199:Actins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D008958:Models, Molecular; D009038:Motion; D009218:Myosins / Q000378:metabolism*; D014335:Tropomyosin / Q000378:metabolism*; D000099163:Myosin Binding Protein C
chemical_list: D000199:Actins; D000255:Adenosine Triphosphate; D002118:Calcium; D002352:Carrier Proteins; D009218:Myosins; D014335:Tropomyosin; D000099163:Myosin Binding Protein C