Engineering stability, longevity, and miscibility of microtubule-based active fluids

Chandrakar, Pooja; Berezney, John P.; Lemma, Bezia; Hishamunda, Bernard; Berry, Angela; Wu, Kun-Ta; Subramanian, Radhika; Chung, Johnson; Needleman, Daniel; Gelles, Jeff; Dogic, Zvonimir

doi:10.1039/d1sm01289d

Cited by 20 publications

(46 citation statements)

References 59 publications

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confidence: 99%

“…In vitro reconstitutions of self-organizing microtubule networks with purified cross-linking motors have provided insight into the basic properties of active microtubule-based networks ( 5 , 6 , 8 – 16 ). Mixtures of microtubules with a single type of cross-linking motor can form extensile, nematic networks in the presence of crowding agents which promote microtubule bundling ( 11 , 16 , 17 ). In the absence of crowding agents, such nematic networks can also form when microtubule densities are relatively high and cross-linking motors bundle microtubules without accumulating at microtubule ends, which happens when the ends grow too fast for motors to reach them ( 6 ).…”

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Cross-linker design determines microtubule network organization by opposing motors

Henkin

Chew

Nédélec

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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During cell division, cross-linking motors determine the architecture of the spindle, a dynamic microtubule network that segregates the chromosomes in eukaryotes. It is unclear how motors with opposite directionality coordinate to drive both contractile and extensile behaviors in the spindle. Particularly, the impact of different cross-linker designs on network self-organization is not understood, limiting our understanding of self-organizing structures in cells but also our ability to engineer new active materials. Here, we use experiment and theory to examine active microtubule networks driven by mixtures of motors with opposite directionality and different cross-linker design. We find that although the kinesin-14 HSET causes network contraction when dominant, it can also assist the opposing kinesin-5 KIF11 to generate extensile networks. This bifunctionality results from HSET’s asymmetric design, distinct from symmetric KIF11. These findings expand the set of rules underlying patterning of active microtubule assemblies and allow a better understanding of motor cooperation in the spindle.

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confidence: 99%

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confidence: 99%

Cross-linker design determines microtubule network organization by opposing motors

Henkin

Chew

Nédélec

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Instead, KIF11 drives persistent sliding of antiparallel microtubules, which in the dense microtubule suspension leads to repeated buckling, merging and sliding of bundles in 3 dimensions (Fig. 1e) 6, 11, 14, 15, 16, 20 . We varied tubulin and KIF11 concentrations (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Biological components with designs optimized for different tasks in living cells offer a variety of “tools” for integration into biomimetic materials, enriching the rulebook by which we understand macroscopic self-organized states, while giving rise to surprising new behaviors 14, 15, 16 . Here, we have shown how motile crosslinkers determine the large-scale properties of an active material and how these properties can be controlled not only by varying crosslinker concentrations, but also crosslinker properties.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro reconstitutions of self-organizing microtubule networks with purified crosslinking motors have provided insight into the basic properties of active microtubule-based materials 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16 . Extensile, nematic networks are promoted by high microtubule densities and growth rates, or the presence of crowding agents, whereas contractile or radially polar networks form when motors can accumulate at microtubule ends 6, 17 .…”

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confidence: 99%

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Crosslinker design determines microtubule network organization by opposing motors

Henkin

Chew

Nédélec

et al. 2022

Preprint

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During cell division, crosslinking motors determine the architecture of the spindle, a dynamic microtubule network that segregates the chromosomes. It is unclear how motors with opposite directionality coordinate to drive both contractile and extensile behaviors in the spindle. Particularly, the impact of different crosslinker designs on network self-organization is not understood, limiting our understanding of self-organizing structures in cells, but also our ability to engineer new active materials. Here, we use experiment and theory to examine active microtubule networks driven by mixtures of motors with opposite directionality and different crosslinker design. We find that although the kinesin-14 HSET causes network contraction when dominant, it can also assist the opposing kinesin-5 KIF11 to generate extensile networks. This bifunctionality results from HSET’s asymmetric design, distinct from symmetric KIF11. These findings expand the set of rules underlying patterning of active microtubule assemblies and allow a better understanding of motor cooperation in the spindle.SIGNIFICANCE STATEMENTDuring cell division, the spindle apparatus segregates duplicated chromosomes for their inheritance by the daughter cells. The spindle is a highly interconnected network of microtubule filaments that are crosslinked by different types of molecular motors. How the different motors cooperate to organize the spindle network is not understood. Here, we show that an asymmetric crosslinker design can confer bifunctionality to a mitotic motor in the presence of other motors. The asymmetric motor supports both extensile and contractile microtubule network behaviors as observed in different parts of the spindle. These findings define new rules controlling the generation of active microtubule networks and allow us to better understand how motors cooperate to organize the correct spindle architecture when a cell divides.

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Competing instabilities reveal how to rationally design and control active crosslinked gels

et al. 2022

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How active stresses generated by molecular motors set the large-scale mechanics of the cell cytoskeleton remains poorly understood. Here, we combine experiments and theory to demonstrate how the emergent properties of a biomimetic active crosslinked gel depend on the properties of its microscopic constituents. We show that an extensile nematic elastomer exhibits two distinct activity-driven instabilities, spontaneously bending in-plane or buckling out-of-plane depending on its composition. Molecular motors play a dual antagonistic role, fluidizing or stiffening the gel depending on the ATP concentration. We demonstrate how active and elastic stresses are set by each component, providing estimates for the active gel theory parameters. Finally, activity and elasticity were manipulated in situ with light-activable motor proteins, controlling the direction of the instability optically. These results highlight how cytoskeletal stresses regulate the self-organization of living matter and set the foundations for the rational design and optogenetic control of active materials.

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Engineering stability, longevity, and miscibility of microtubule-based active fluids

Abstract: Microtubule-based active matter provides insight into the self-organization of motile interacting constituents. We describe several formulations of microtubule-based 3D active isotropic fluids. Dynamics of these fluids is powered by three...

Cited by 20 publications

References 59 publications

Cross-linker design determines microtubule network organization by opposing motors

Cross-linker design determines microtubule network organization by opposing motors

Crosslinker design determines microtubule network organization by opposing motors

Competing instabilities reveal how to rationally design and control active crosslinked gels

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