What are the forces driving the growth and maturation of axons and dendrites in neurons?

Axons and dendrites, the prominent structures emanating from the cell body of neurons, are the processes responsible for the transmission and reception of electrical signals through the nervous system. While the structure of individual neurons is a key to the function of a neuronal network, still very little is known on how it develops on the mechanical and molecular levels. A major factor in the cytoskeleton of axons and dendrites are dense bundles of microtubules that run across their length, providing tracks for molecular motors to transmit vesicles filled by nutrients and other factors from the cell body outwards and vice versa. In addition, those heavily dense microtubule bundles and the molecular motors that bind them, are believed to play a key role in driving the growth and maturation of neurons. The sliding motion of molecular motors along microtubules not only drives the filaments' motion but also contributes to their sorting along the process. However, a quantitative understanding of how the ensembles of molecular motors and cytoskeleton filaments cooperate to produce forces and structure in neuronal processes is still lacking. To investigate these questions we develop computer simulations that allow us to calculate the dynamics of filaments in bundles of microtubules that are cross-linked and powered by molecular motors. The motion of filaments and the forces they exert are investigated as a function of the motor type, the microtubule density and length, applied load and motor connectivity. The work is carried out in close collaboration with the experimental group of Kristian Franze at Cambridge University.

To read more about this project see: 

Jakobs, Maximilian, Kristian Franze, and Assaf Zemel. 2015. “Force Generation By Molecular-Motor-Powered Microtubule Bundles; Implications For Neuronal Polarization And Growth.” Frontiers In Cellular Neuroscience 9: 441

Jakobs, Maximilian, Kristian Franze, and Assaf Zemel. 2020. “Mechanical Regulation of Neurite Polarization and Growth: A Computational Study.” Biophysical Journal, in press