Mechanochemical regulation of growth cone motility

Abstract

Neuronal growth cones are exquisite sensory-motor machines capable of transducing features contacted in their local extracellular environment into guided process extension during development. Extensive research has shown that chemical ligands activate cell surface receptors on growth cones leading to intracellular signals that direct cytoskeletal changes. However, the environment also provides mechanical support for growth cone adhesion and traction forces that stabilize leading edge protrusions. Interestingly, recent work suggests that both the mechanical properties of the environment and mechanical forces generated within growth cones influence axon guidance. In this review we discuss novel molecular mechanisms involved in growth cone force production and detection, and speculate how these processes may be necessary for the development of proper neuronal morphogenesis.

Scale Invariant Disordered Nanotopography Promotes Hippocampal Neuron Development and Maturation with Involvement of Mechanotransductive Pathways

“…The capacity of biomaterials to modulate cellular functions relies on the cellular competence for mechanotransduction; i.e., the perception of microenvironmental biophysical signals (rigidity and nanotopography) and the subsequent conversion into corresponding cellular responses via mechanosensitive cell components (Wang et al, 2009; Dalby et al, 2014; Murphy et al, 2014; Chen et al, 2015). The phenomen of cellular biomechanics, in particular its involvement in neurogenesis and neuronal development, has attracted considerable interest in the last years (Tyler, 2012; Franze et al, 2013; Kerstein et al, 2015). …”

“…The importance of neuron/ECM interaction for neurogenic events is well-documented (Pizzorusso et al, 2002; de Curtis, 2007; Dityatev et al, 2010; Myers et al, 2011; Kerstein et al, 2015). Neural circuit development critically depends on the generation of well-defined dendritic and axonal structures and their eventual reciprocal interactions leading to functional synaptic junctions (Benson et al, 2001; Graf et al, 2004; Nam and Chen, 2005; Sara et al, 2005).…”

“…These developmental processes are largely controlled by extracellular cues which can be diffusible but often they are bound to cell membranes or are part of the ECM providing attractive, repulsive, or retaining signals like e.g., in the perineuronal nets. Especially the outgrowth/guidance of axons and the synaptic plasticity are modulated by a spatiotemporally dynamic interaction with the substrate (Benson et al, 2001; Pizzorusso et al, 2002; Craig et al, 2006; de Curtis, 2007; Dityatev et al, 2010; Myers et al, 2011; Vitriol and Zheng, 2012; Geissler et al, 2013; Bikbaev et al, 2015; Kerstein et al, 2015). For the exploration of the microenvironment integrin-mediated point contacts play an essential role by linking the ECM to the neuronal actin cytoskeleton which enables force generation and mechanotransduction.…”

Cell adhesion and invasion mechanisms that guide developing axons

“…PCs stabilize filopodial protrusions and remain fixed in position during growth cone advance, but turnover quickly in rapidly extending axons [34, 35]. Similar to mesenchymal migration, the formation and dynamic turnover of PC adhesions at the growth cone periphery correlates with the rate of axon outgrowth and is regulated by both the cell substratum and soluble growth factors [4, 36]. Many axon guidance cues are known to operate by regulating integrin-mediated adhesion [37–44].…”

Mathematical modelling of axon guidance in chemical gradients

“…It is being pulled by tension from the axon but it is this tension that stimulates growth and elongation through some little understood mechanosensing mechanism. Some progress has been made in revealing the mechanisms underlying this process [286]. Through the coupling with the substrate, the retrograde flow of actin within the growth cone drives its movement forward.…”