Conformational Dynamics and Thermal Cones of C-terminal Tubulin Tails in Neuronal Microtubules

In this paper we present a model for estimation of the C-terminal tubulin tail (CTT) dynamics in cytoskeletal microtubules of nerve cells. We show that the screened Coulomb interaction between a target CTT and the negatively charged microtubule surface as well as its immediate CTT neighbours results in confinement of the CTT motion within a restricted volume referred to as a thermal cone. Within the thermal cone the CTT motion is driven by the thermal fluctuations, while outside the thermal cone the CTT interaction energy with its environment is above the thermal energy solely due to repulsion from the negatively charged microtubule surface. Computations were performed for different CTT geometries and we have found that the CTT conformation with lowest energy is perpendicular to the microtubule surface. Since the coupling between a target CTT with its neighbour CTTs is 8 orders of magnitude below the thermal energy and considering the extremely short cytosolic Debye length of 0.79 nm, our results rule out generation and propagation of CTT conformational waves along the protofilament as a result of local CTT perturbations. The results as presented support a model in which the cytosolic electric fields and ionic currents generated by the neuronal excitations are “projected” onto the CTTs of underlying microtubules thus affecting their regulatory function upon kinesin motion and MAP attachment/detachment. Originally published in Neuroquantology 2007; 5(1): 62-84.