Microscopic interactions control a structural transition in active mixtures of microtubules and molecular motors

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 121; no. 2; p. e2300174121
• Main Authors: Najma, Bibi, Wei, Wei-Shao, Baskaran, Aparna, Foster, Peter J, Duclos, Guillaume
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09.01.2024
• Subjects: Accumulation; Adenosine; Cell Movement; Chromosome Segregation; Chromosomes; Clusters; Contractility; Crosslinking; Cytoskeleton; Cytoskeleton - metabolism; Depletion; Gels; Kinesin; Kinesins - metabolism; Kinetics; Microtubules; Microtubules - metabolism; Molecular motors; Parameter identification; Physical Sciences; Proteins; Robust control; Self-assembly; Time; self-organization; microtubules; active matter; molecular motors
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2300174121

Microtubules and molecular motors are essential components of the cellular cytoskeleton, driving fundamental processes in vivo, including chromosome segregation and cargo transport. When reconstituted in vitro, these cytoskeletal proteins serve as energy-consuming building blocks to study the self-organization of active matter. Cytoskeletal active gels display rich emergent dynamics, including extensile flows, locally contractile asters, and bulk contraction. However, it is unclear how the protein-protein interaction kinetics set their contractile or extensile nature. Here, we explore the origin of the transition from extensile bundles to contractile asters in a minimal reconstituted system composed of stabilized microtubules, depletant, adenosine 5'-triphosphate (ATP), and clusters of kinesin-1 motors. We show that the microtubule-binding and unbinding kinetics of highly processive motor clusters set their ability to end-accumulate, which can drive polarity sorting of the microtubules and aster formation. We further demonstrate that the microscopic time scale of end-accumulation sets the emergent time scale of aster formation. Finally, we show that biochemical regulation is insufficient to fully explain the transition as generic aligning interactions through depletion, cross-linking, or excluded volume interactions can drive bundle formation despite end-accumulating motors. The extensile-to-contractile transition is well captured by a simple self-assembly model where nematic and polar aligning interactions compete to form either bundles or asters. Starting from a five-dimensional organization phase space, we identify a single control parameter given by the ratio of the different component concentrations that dictates the material-scale organization. Overall, this work shows that the interplay of biochemical and mechanical tuning at the microscopic level controls the robust self-organization of active cytoskeletal materials.