title: Membrane tension, myosin force, and actin turnover maintain actin treadmill in the nerve growth cone.
abstract: A growth cone is a motile structure at the tips of axons that is driven by the actin network and guides axon extension. Low actin adhesion to the substrate creates a stationary actin treadmill that allows leading-edge protrusion when adhesion increases in response to guidance cues. We use experimental measurements in the Aplysia bag growth cone to develop and constrain a simple mechanical model of the actin treadmill. We show that actin retrograde flow is primarily generated by myosin contractile forces, but when myosin is inhibited, leading-edge membrane tension increases and drives the flow. By comparing predictions of the model with previous experimental measurements, we demonstrate that lamellipodial and filopodial filament breaking contribute equally to the resistance to the flow. The fully constrained model clarifies the role of actin turnover in the mechanical balance driving the actin treadmill and reproduces the recent experimental observation that inhibition of actin depolymerization causes retrograde flow to slow exponentially with time. We estimate forces in the actin treadmill, and we demonstrate that measured G-actin distributions are consistent with the existence of a forward-directed fluid flow that transports G-actin to the leading edge.
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, California, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Craig
authors.forename: David
authors.initials: D
authors.lastname: Van Goor
authors.forename: Paul
authors.initials: P
authors.lastname: Forscher
authors.forename: Alex
authors.initials: A
authors.lastname: Mogilner
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D001696:Biomechanical Phenomena; D002462:Cell Membrane / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism*; D007700:Kinetics; D055595:Mechanical Phenomena; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011554:Pseudopodia / Q000378:metabolism
chemical_list: D000199:Actins; D009218:Myosins