Abstract
Robustness of biological systems is crucial for their survival, however, for many systems its origin is an open question. Here, we analyze one subcellular level system, the microtubule cytoskeleton. Microtubules self-organize into a network, along which cellular components are delivered to their biologically relevant locations. While the dynamics of individual microtubules is sensitive to the organism's environment and genetics, a similar sensitivity of the overall network would result in pathologies. Our large-scale stochastic simulations show that the self-organization of microtubule networks is robust in a wide parameter range in individual cells. We confirm this robustness in vivo on the tissue-scale using genetic manipulations of Drosophila epithelial cells. Finally, our minimal mathematical model shows that the origin of robustness is the separation of time-scales in microtubule dynamics rates. Altogether, we demonstrate that the tissue-scale self-organization of a microtubule network depends only on cell geometry and the distribution of the microtubule minus-ends.
Highlights
The correct positioning of intracellular components such as proteins and organelles is critical for correct cellular function (St Johnston and Ahringer, 2010; Ryder and Lerit, 2018)
The dynamics and number of individual microtubules in a cell depend on the expression of particular plus- and minus-end binding proteins (Akhmanova and Steinmetz, 2015), the interaction between microtubules is affected by the presence of crosslinking and motor proteins (Kapitein and Hoogenraad, 2015), and the stability of the microtubule network is affected by external factors, e.g. temperature, which changes microtubule rigidity (Kawaguchi and Yamaguchi, 2010)
We explore the self-organization of bidirectional microtubule networks, which are common in differentiated epithelial cells – one of the four fundamental tissue types found in all animals (Gilbert et al, 1991; Bulgakova et al, 2013; Muroyama and Lechler, 2017; Tateishi et al, 2017)
Summary
The correct positioning of intracellular components such as proteins and organelles is critical for correct cellular function (St Johnston and Ahringer, 2010; Ryder and Lerit, 2018) These components are transported to their biologically relevant locations by motor proteins moving along the cytoskeleton (Gagnon and Mowry, 2011; Kapitein and Hoogenraad, 2011; Franker and Hoogenraad, 2013), or through active diffusion often dependent on these motors (Drechsler et al, 2017; Colin et al, 2020). One common type of cytoskeleton used for transport is microtubules (Franker and Hoogenraad, 2013) These are highly dynamic unstable polymers that switch between periods of growth and shrinkage. The dynamics and number of individual microtubules in a cell depend on the expression of particular plus- and minus-end binding proteins (Akhmanova and Steinmetz, 2015), the interaction between microtubules is affected by the presence of crosslinking and motor proteins (Kapitein and Hoogenraad, 2015), and the stability of the microtubule network is affected by external factors, e.g. temperature, which changes microtubule rigidity (Kawaguchi and Yamaguchi, 2010)
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