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Neuronal growth cones are the most sensitive amongst eukaryotic cells inresponding to directional chemical cues. Although a dynamic microtubulecytoskeleton has been shown to be essential for growth cone turning, theprecise nature of coupling of the spatial cue with microtubule polarization isless understood. Here we present a computational model of microtubulepolarization in a turning neuronal growth cone (GC). We explore the limits ofdirectional cues in modifying the spatial polarization of microtubules bytesting the role of microtubule dynamics, gradients of regulators andretrograde forces along filopodia. We analyze the steady state and transitionbehavior of microtubules on being presented with a directional stimulus. Themodel makes novel predictions about the minimal angular spread of the chemicalsignal at the growth cone and the fastest polarization times. A regulatoryreaction-diffusion network based on the cyclicphosphorylation-dephosphorylation of a regulator predicts that the receptorsignal magnitude can generate the maximal polarization of microtubules and notfeedback loops or amplifications in the network. Using both thephenomenological and network models we have demonstrated some of the physicallimits within which the MT polarization system works in turning neuron.

Spatial and Temporal Sensing Limits of Microtubule Polarization in Neuronal Growth Cones by Intracellular Gradients and Forces