title: Force Generation by Membrane-Associated Myosin-I.
abstract: Vertebrate myosin-IC (Myo1c) is a type-1 myosin that links cell membranes to the cytoskeleton via its actin-binding motor domain and its phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-binding tail domain. While it is known that Myo1c bound to PtdIns(4,5)P2 in fluid-lipid bilayers can propel actin filaments in an unloaded motility assay, its ability to develop forces against external load on actin while bound to fluid bilayers has not been explored. Using optical tweezers, we measured the diffusion coefficient of single membrane-bound Myo1c molecules by force-relaxation experiments, and the ability of ensembles of membrane-bound Myo1c molecules to develop and sustain forces. To interpret our results, we developed a computational model that recapitulates the basic features of our experimental ensemble data and suggests that Myo1c ensembles can generate forces parallel to lipid bilayers, with larger forces achieved when the myosin works away from the plane of the membrane or when anchored to slowly diffusing regions.
authors.affiliation: The Pennsylvania Muscle Institute and Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia PA 19104-6085, USA.
authors.forename: Serapion
authors.initials: S
authors.lastname: Pyrpassopoulos
authors.affiliation: Department of Physics, Worcester Polytechnic Institute, Worcester MA 01609, USA.
authors.forename: Göker
authors.initials: G
authors.lastname: Arpağ
authors.affiliation: The Pennsylvania Muscle Institute and Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia PA 19104-6085, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Feeser
authors.affiliation: The Pennsylvania Muscle Institute and Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia PA 19104-6085, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Shuman
authors.affiliation: Department of Physics, Worcester Polytechnic Institute, Worcester MA 01609, USA.
authors.forename: Erkan
authors.initials: E
authors.lastname: Tüzel
authors.affiliation: The Pennsylvania Muscle Institute and Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia PA 19104-6085, USA.
authors.forename: E Michael
authors.initials: EM
authors.lastname: Ostap
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D002462:Cell Membrane / Q000378:metabolism*; D003198:Computer Simulation; D004058:Diffusion; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D024461:Myosin Type I / Q000378:metabolism*; D052898:Optical Tweezers; D021381:Protein Transport
chemical_list: D000199:Actins; D008055:Lipids; C470422:Myo1c protein, mouse; D024461:Myosin Type I