Remarkable structural transformations of actin bundles are driven by their initial polarity, motor activity, crosslinking, and filament treadmilling

by Aravind Chandrasekaran, Arpita Upadhyaya, Garegin A. Papoian

Bundled actin structures play a key role in maintaining cellular shape, in aiding force transmission to and from extracellular substrates, and in affecting cellular motility. Recent studies have also brought to light new details on stress generation, force transmission and contractility of actin bundles. In this work, we are primarily interested in the question of what determines the stability of actin bundles and what network geometries do unstable bundles eventually transition to. To address this problem, we used the MEDYAN mechano-chemical force field, modeling several micron-long actin bundles in 3D, while accounting for a comprehensive set of chemical, mechanical and transport processes. We developed a hierarchical clustering algorithm for classification of the different long time scale morphologies in our study. Our main finding is that initially unipolar bundles are significantly more stable compared with an apolar initial configuration. Filaments within the latter bundles slide easily with respect to each other due to myosin activity, producing a loose network that can be subsequently severely distorted. At high myosin concentrations, a morphological transition to aster-like geometries was observed. We also investigated how actin treadmilling rates influence bundle dynamics, and found that enhanced treadmilling leads to network fragmentation and disintegration, while this process is opposed by myosin and crosslinking activities. Interestingly, treadmilling bundles with an initial apolar geometry eventually evolve to a whole gamut of network morphologies based on relative positions of filament ends, such as sarcomere-like organization. We found that apolar bundles show a remarkable sensitivity to environmental conditions, which may be important in enabling rapid cytoskeletal structural reorganization and adaptation in response to intracellular and extracellular cues.

Tratto da: www.plos.org
Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.