Growth cone behavior and production of traction force.

Abstract

Abstract. The growth cone must push its substrate rearward via some traction force in order to propel itself forward. To determine which growth cone behaviors produce traction force, we observed chick sensory growth cones under conditions in which force production was accommodated by movement of obstacles in the environment, namely, neurites of other sensory neurons or glass fibers. The movements of these obstacles occurred via three, different, stereotyped growth cone behaviors: (a) filopodial contractions, (b) smooth rearward movement on the dorsal surface of the growth cone, and (c) interactions with ruffling lamellipodia. More than 70% of the obstacle movements were caused by filopodial contractions in which the obstacle attached at the extreme distal end of a filopodium and moved only as the filopodium changed its extension. Filopodial contractions were characterized by frequent changes of obstacle velocity and direction. Contraction of a single filopodium is estimated to exert 50-90/~dyn of force, which can account for the pull exerted by chick sensory growth cones. Importantly, all five cases of growth cones growing over the top of obstacle neurites (i.e., geometry that mimics the usual growth cone/substrate interaction), were of the filopodial contraction type. Some 25 % of obstacle movements occurred by a smooth backward movement along the top surface of growth cones. Both the appearance and rate of movements were similar to that reported for retrograde flow of cortical actin near the dorsal growth cone surface. Although these retrograde flow movements also exerted enough force to account for growth cone pulling, we did not observe such movements on ventral growth cone surfaces. Occasionally obstacles were moved by interaction with ruffling lamellipodia. However, we obtained no evidence for attachment of the obstacles to ruffling lamellipodia or for directed obstacle movements by this mechanism. These data suggest that chick sensory growth cones move forward by contractile activity of filopodia, i.e., isometric contraction on a rigid substrate. Our data argue against retrograde flow of actin producing traction force.

Extreme Stretch Growth of Integrated Axons

“…From these observations, it was proposed that tension from locomotor activity of growth cones is an important regulator of axon outgrowth. Thus, tension may be a key modulator for two distinct forms of axonal growth that act in continuum; initially, growth cones slowly pull individual axons to reach their targets (Bray, 1979;Heidemann et al, 1990), followed by stretch growth, which forces large populations of integrated axons to grow in unison at enormous rates over long periods of time (Weiss, 1941;Bray, 1984).…”

Mechanotransduction – a field pulling together?

“…In the presence of strong adhesion against an underlying substrate, these filaments tend to coalesce into stress fibers that are tethered at sites of adhesion (Chrzanowska-Wodnicka and Burridge, 1996). Although I will focus exclusively on myosin-regulated contractile forces, it is possible that other signals that alter actin polymerization and organization also alter force, and that other cytoskeletal elements such as microtubules also contribute to net forces (Dogterom and Yurke, 1997;Stamenovic et al, 2002;Reinhart-King et al, 2005;Prass et al, 2006;Heidemann et al, 1990).…”

Characterization of neural cell adhesion sites: point contacts are the sites of interaction between integrins and the cytoskeleton in PC12 cells

“…We reason, then, that integrins on filopodia extending unattached from the margins of growth cones have integrins uniformly in small aggregates on their surfaces. Interaction with an immobilized ligand then triggers association with the cytoskeleton and, possibly at the same time, contractile events responsible for pulling (Heidemann et al, 1990) the growth cone over the substratum.…”