Jeffrey Urbach

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  Biomechanics and Dynamics of Growth Cones in Engineered Environments
  Jeffrey Urbach

  In the developing nervous system, axons respond to a diverse array of cues to generate the intricate connection network required for proper function. The growth cone integrates information about the local environment and modulates outgrowth and guidance, but relatively little is known about effects of external mechanical or structural cues and internal mechanical forces on growth cone behavior. We have investigated axon outgrowth and force generation on soft elastic substrates for dorsal root ganglion (DRG) neurons (from the peripheral nervous system) and hippocampal neurons (from the central) to see how the mechanics of the microenvironment affect different populations. We find that force generation and stiffness-dependent outgrowth are strongly dependent on cell type. I will discuss recent analyses of the dynamic aspects of growth cone force generation that show surprising regularity underlying the dynamic pattern of traction forces. I will also describe experiments showing that micron-scale confinement affects growth cone shape but, surprisingly, not neurite growth rates. Changes in confinement, by contrast, produce dramatic changes in extension rates. These results suggest a range of opportunities and challenges for developing a quantitative understanding of the influence on engineered environments on axon growth and guidance.