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1. Non-specific cargo–filament interactions slow down motor-driven transport

   https://doi.org/10.1140/epje/s10189-023-00394-4  

   Labastide, Joelle A; Quint, David A; Cullen, Reilly K; Maelfeyt, Bryan; Ross, Jennifer L; Gopinathan, Ajay (December 2023, The European Physical Journal E)

   Active, motor-based cargo transport is important for many cellular functions and cellular development. However, the cell interior is complex and crowded and could have many weak, non-specific interactions with the cargo being transported. To understand how cargo-environment interactions will affect single motor cargo transport and multi-motor cargo transport, we use an artificial quantum dot cargo bound with few (~ 1) to many (~ 5–10) motors allowed to move in a dense microtubule network. We find that kinesin-driven quantum dot cargo is slower than single kinesin-1 motors. Excitingly, there is some recovery of the speed when multiple motors are attached to the cargo. To determine the possible mechanisms of both the slow down and recovery of speed, we have developed a computational model that explicitly incorporates multi-motor cargos interacting non-specifically with nearby microtubules, including, and predominantly with the microtubule on which the cargo is being transported. Our model has recovered the experimentally measured average cargo speed distribution for cargo-motor configurations with few and many motors, implying that numerous, weak, non-specific interactions can slow down cargo transport and multiple motors can reduce these interactions thereby increasing velocity. 

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2. The battle between internal and external forces in microtubule-kinesin active fluid

   Wu, Kun-Ta; Dickie, Joshua; Weng, Tianxing; Chen, Yen-Chen; He, Yutian; Saxena, Saloni; Pelcovits, Robert; Powers, Thomas (March 2025, Bulletin of the American Physical Society)

   Microtubule-kinesin active fluids consume ATP to generate internal active stresses, driving spontaneous and complex flows. While numerous studies have explored the fluid's autonomous behavior, its response to external mechanical forces remains less understood. This study explores how moving boundaries affect the flow dynamics of this active fluid when confined in a thin cuboidal cavity. Our experiments demonstrate a transition from chaotic, disordered vortices to a single, coherent system-wide vortex as boundary speed increases, resembling the behavior of passive fluids like water. Furthermore, our confocal microscopy revealed that boundary motion altered the microtubule network structure near the moving boundary. In the absence of motion, the network exhibited a disordered, isotropic configuration. However, as the boundary moved, microtubule bundles aligned with the shear flow, resulting in a thicker, tilted nematic layer extending over a greater distance from the moving boundary. These findings highlight the competing influences of external shear stress and internal active stress on both flow kinematics and microtubule network structure. This work provides insight into the mechanical properties of active fluids, with potential applications in areas such as adaptive biomaterials that respond to mechanical stimuli in biological environments. 

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3. Active nematic order and dynamic lane formation of microtubules driven by membrane-bound diffusing motors

   https://doi.org/10.1073/pnas.2117107118  

   Memarian, Fereshteh L.; Lopes, Joseph D.; Schwarzendahl, Fabian Jan; Athani, Madhuvanthi Guruprasad; Sarpangala, Niranjan; Gopinathan, Ajay; Beller, Daniel A.; Dasbiswas, Kinjal; Hirst, Linda S. (December 2021, Proceedings of the National Academy of Sciences)

   Dynamic lane formation and long-range active nematic alignment are reported using a geometry in which kinesin motors are directly coupled to a lipid bilayer, allowing for in-plane motor diffusion during microtubule gliding. We use fluorescence microscopy to image protein distributions in and below the dense two-dimensional microtubule layer, revealing evidence of diffusion-enabled kinesin restructuring within the fluid membrane substrate as microtubules collectively glide above. We find that the lipid membrane acts to promote filament–filament alignment within the gliding layer, enhancing the formation of a globally aligned active nematic state. We also report the emergence of an intermediate, locally ordered state in which apolar dynamic lanes of nematically aligned microtubules migrate across the substrate. To understand this emergent behavior, we implement a continuum model obtained from coarse graining a collection of self-propelled rods, with propulsion set by the local motor kinetics. Tuning the microtubule and kinesin concentrations as well as active propulsion in these simulations reveals that increasing motor activity promotes dynamic nematic lane formation. Simulations and experiments show that, following fluid bilayer substrate mediated spatial motor restructuring, the total motor concentration becomes enriched below the microtubule lanes that they drive, with the feedback leading to more dynamic lanes. Our results have implications for membrane-coupled active nematics in vivo as well as for engineering dynamic and reconfigurable materials where the structural elements and power sources can dynamically colocalize, enabling efficient mechanical work. 

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4. The battle between internal and external forces in microtubule-kinesin active fluid

   Wu, Kun-Ta; Dickie, Joshua H; Weng, Tianxing; Chen, Yen-Chen; He, Yutian; Saxena, Saloni; Pelcovits, Robert A; Powers, Thomas R (October 2024, Bulletin of the American Physical Society)

   Microtubule-kinesin active fluids consume ATP to generate internal active stresses, driving spontaneous and complex flows. While numerous studies have explored the fluid's autonomous behavior, its response to external mechanical forces remains less understood. This study explores how moving boundaries affect the flow dynamics of this active fluid when confined in a thin cuboidal cavity. Our experiments demonstrate a transition from chaotic, disordered vortices to a single, coherent system-wide vortex as boundary speed increases, resembling the behavior of passive fluids like water. Furthermore, our confocal microscopy revealed that boundary motion altered the microtubule network structure near the moving boundary. In the absence of motion, the network exhibited a disordered, isotropic configuration. However, as the boundary moved, microtubule bundles aligned with the shear flow, resulting in a thicker, tilted nematic layer extending over a greater distance from the moving boundary. These findings highlight the competing influences of external shear stress and internal active stress on both flow kinematics and microtubule network structure. This work provides insight into the mechanical properties of active fluids, with potential applications in areas such as adaptive biomaterials that respond to mechanical stimuli in biological environments. *We acknowledge support from the National Science Foundation (NSF-CBET-2045621). This research is performed with computational resources supported by the Academic & Research Computing Group at Worcester Polytechnic Institute. We acknowledge the Brandeis Materials Research Science and Engineering Center (NSF-MRSEC-DMR-2011846) for use of the Biological Materials Facility. 

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5. Complex nearly immotile behaviour of enzymatically driven cargos

   https://doi.org/10.1039/c8sm01893f  

   Osunbayo, O.; Miles, C. E.; Doval, F.; Reddy, B. J.; Keener, J. P.; Vershinin, M. D. (February 2019, Soft Matter)

   We report a minimal microtubule-based motile system displaying signatures of unconventional diffusion. The system consists of a single model cargo driven by an ensemble of N340K NCD motors along a single microtubule. Despite the absence of cytosolic or cytoskeleton complexity, the system shows complex behavior, characterized by sub-diffusive motion for short time lag scales and linear mean squared displacement dependence for longer time lags. The latter is also shown to have non-Gaussian character and cannot be ascribed to a canonical diffusion process. We use single particle tracking and analysis at varying temperatures and motor concentrations to identify the origin of these behaviors as enzymatic activity of mutant NCD. Our results show that signatures of non-Gaussian diffusivities can arise as a result of an active process and suggest that some immotility of cargos observed in cells may reflect the ensemble workings of mechanochemical enzymes and need not always reflect the properties of the cytoskeletal network or the cytosol. 

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