Branching, crosslinking and decentralization of microtubules accelerates intracellular assembly

Abstract

Before cell division, mitotic spindle is assembled from chromosomes and centrosomes. After the cell division, Golgi organelles assemble from multiple vesicles scattered across daughter cells. These are but two examples of intracellular assembly of vesicles, organelles and chromosomes made possible by dynamic microtubules. The most prominent microtubule networks are centrosome-focused asters that search for the vesicles and chromosomes, but there are also microtubules originating from the vesicles and chromosomes, raising the question whether a coordination between multiple microtubule networks optimizes the assembly process. This study uses a computational model to examine how microtubule dynamics influence the assembly of organelles from vesicles. The model includes two microtubule populations: microtubules anchored to the vesicles, which drive local clustering, and central microtubules anchored to the centrosome that aggregate the vesicles globally. Simulations show that a microtubule decentralization - balanced contribution from both microtubule populations -- accelerates the assembly of tens of vesicles, but that assigning all microtubules to hundreds of vesicles optimizes the assembly. Directionally biased microtubule growth, particularly when avoiding spontaneous catastrophe events, further accelerates the assembly. Additionally, microtubule branching, when occurring at optimal angles and spacings, enhances the assemblys efficiency. Lastly, rapid crosslinking of overlapping central and local microtubules can drastically accelerate the assembly. Applying this model to the spindle assembly in early mitosis reveals similar insights. The model suggests that the observed multiple microtubule networks optimize the intracellular assembly processes when molecular resources are limited. SIGNIFICANCEAssembly of intracellular structures is a time-sensitive process driven by multiple dynamic microtubule networks. For example, vesicles must be aggregated by microtubules to form Golgi apparatus after cell division, while mitotic spindle assembly requires bringing chromosomes closer together by microtubules growing from spindle poles and chromosomes. Delays in these processes can lead to genomic instability and disease. Using modeling, we show how microtubules originating from centrosomes, vesicles, or chromosomes can be optimally distributed to minimize the assembly time. The model reveals roles of microtubule decentralization, branching and crosslinking in accelerating assembly. The model suggests that the intracellular assembly can be optimized by diversifying microtubule networks and enhancing their interactions.