publications

2025

1. Analysis of disordered trusses using network Laplacian

   Niranjan Sarpangala, Sean Fancher, Prashant K Purohit, and 1 more author

   arXiv, submitted to the Soft Matter journal, 2025

   S. Fancher and N. Sarpangala contributed equally to work.

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2. Gliding microtubules exhibit tunable collective rotation driven by chiral active forces

   Madhuvanthi Guruprasad Athani, Nathan Prouse, Niranjan Sarpangala, and 9 more authors

   arXiv, submitted to PNAS, 2025

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3. Heterogeneity in single motor velocity is essential to explain enhanced velocity of membrane-bound cargoes

   Niranjan Sarpangala and Ajay Gopinathan

   bioRxiv, submitted to the Biophysical journal, 2025

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2024

1. Tunable intracellular transport on converging microtubule morphologies

   Niranjan Sarpangala, Brooke Randell, Ajay Gopinathan, and 1 more author

   Biophysical Reports, 2024

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   A common type of cytoskeletal morphology involves multiple microtubules converging with their minus ends at the microtubule organizing center (MTOC). The cargo-motor complex will experience ballistic transport when bound to microtubules or diffusive transport when unbound. This machinery allows for sequestering and subsequent dispersal of dynein-transported cargo. The general principles governing dynamics, efficiency, and tunability of such transport in the MTOC vicinity are not fully understood. To address this, we develop a one-dimensional model that includes advective transport toward an attractor (such as the MTOC) and diffusive transport that allows particles to reach absorbing boundaries (such as cellular membranes). We calculated the mean first passage time (MFPT) for cargo to reach the boundaries as a measure of the effectiveness of sequestering (large MFPT) and diffusive dispersal (low MFPT). We show that the MFPT experiences a dramatic growth, transitioning from a low to high MFPT regime (dispersal to sequestering) over a window of cargo on-/off-rates that is close to in vivo values. Furthermore, increasing either the on-rate (attachment) or off-rate (detachment) can result in optimal dispersal when the attractor is placed asymmetrically. Finally, we also describe a regime of rare events where the MFPT scales exponentially with motor velocity and the escape location becomes exponentially sensitive to the attractor positioning. Our results suggest that structures such as the MTOC allow for the sensitive control of the spatial and temporal features of transport and corresponding function under physiological conditions.

2023

1. Effects of Cytoskeletal Network Mesh Size on Cargo Transport

   Nimisha Krishnan, Niranjan Sarpangala, Maria Gamez, and 2 more authors

   The European Physical Journal E, 2023

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   Intracellular transport of cargoes in the cell is essential for the organization and functioning cells, especially those that are large and elongated. The cytoskeletal networks inside large cells can be highly complex, and this cytoskeletal organization can have impacts on the distance and trajectories of travel. Here, we experimentally created microtubule networks with varying mesh sizes and examined the ability of kinesin-driven quantum dot cargoes to traverse the network. Using the experimental data, we deduced parameters for cargo detachment at intersections and away from intersections, allowing us to create an analytical theory for the run length as a function of mesh size. We also used these parameters to perform simulations of cargoes along paths extracted from the experimental networks. We find excellent agreement between the trends in run length, displacement, and trajectory persistence length comparing the experimental and simulated trajectories.

2. Effect of lipid membranes on intracellular cargo transport by teams of molecular motors

   Niranjan Sarpangala

   University of California, Merced, 2023

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2022

1. Cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors

   Niranjan Sarpangala and Ajay Gopinathan

   Plos Computational Biology, 2022

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   In cells, multiple molecular motors work together as teams to carry cargoes such as vesicles and organelles over long distances to their destinations by stepping along a network of cytoskeletal filaments. How motors that typically mechanically interfere with each other, work together as teams is unclear. Here we explored the possibility that purely physical mechanisms, such as cargo surface fluidity, may potentially enhance teamwork, both at the single motor and cargo level. To explore these mechanisms, we developed a three dimensional simulation of cargo transport along microtubules by teams of kinesin-1 motors. We accounted for cargo membrane fluidity by explicitly simulating the Brownian dynamics of motors on the cargo surface and considered both the load and ATP dependence of single motor functioning. Our simulations show that surface fluidity could lead to the reduction of negative mechanical interference between kinesins and enhanced load sharing thereby increasing the average duration of single motors on the filament. This, along with a cooperative increase in on-rates as more motors bind leads to enhanced collective processivity. At the cargo level, surface fluidity makes more motors available for binding, which can act synergistically with the above effects to further increase transport distances though this effect is significant only at low ATP or high motor density. Additionally, the fluid surface allows for the clustering of motors at a well defined location on the surface relative to the microtubule and the fluid-coupled motors can exert more collective force per motor against loads. Our work on understanding how teamwork arises in cargo-coupled motors allows us to connect single motor properties to overall transport, sheds new light on cellular processes, reconciles existing observations, encourages new experimental validation efforts and can also suggest new ways of improving the transport of artificial cargo powered by motor teams.

2021

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

   Fereshteh L. Memarian, Joseph D. Lopes, Fabian Jan Schwarzendahl, and 6 more authors

   Proceedings of the National Academy of Sciences, 2021

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   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.