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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Craig EM,Van Goor D,Forscher P,Mogilner A

doi

10.1016/j.bpj.2012.03.003

subject

Has Abstract

pub_date

2012-04-04 00:00:00

pages

1503-13

issue

7

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(12)00283-4

journal_volume

102

pub_type

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