Storage and Abrupt Release of Elastic Energy in the Microtubule-EG5 Network

Abstract

Microtubules (MTs) in cells form hierarchical network structure and play important roles in various cellular activities. They emerge as the result of the interactions between MTs and various types of MT-binding proteins, and dynamically changes their structures during cell cycles and according to physiological roles of the cell. To obtain an integrative perspective of the MT networks, we performed reconstruction of the MT networks by using MTs and bipolar kinesin, Eg5. Human Eg5 expressed by HEK293 cells moved processively on an MT at ca. 10 nm/s and had ability to bundle MTs in parallel and anti-parallel manners. When MTs and Eg5 were mixed above the critical concentrations of 1 μM and 1 nM, respectively, the mixture generated various types of network architecture depending on the kinesin-MT mixing ratios. At the low ratios ( 20-hours. Increase to 1:250 made the network contractile with two distinct phases: early slow contraction followed by the abrupt shortening and rupture of the network. Further increase to 1:40, MT networks rapidly contracted into large aggregate immediately after addition of ATP. In contrast, modulation of motor property by using recombinant Eg5 with four heads replaced by faster kinesin (KIF5B, 140 nm/s) heads led to generate a large number of asters. A coarse-grained mathematical model reproduced the network dynamics experimentally observed and delivered a comprehensive picture on the range and diversity of Eg5-MT networks at different spatiotemporal scales. We also calculated the elastic energy stored in the networks, and found that it is accumulated through early contractions in the active network, and can be released into mechanical work during rupturing. This feature might play some roles in the initiation of cell locomotion. (Supported by CREST, JST).