Intracellular transport of vesicles and organelles, which is essential for maintaining spatial organization within eukaryotic cells is typically carried out by a combination of diffusion and active, motor-driven transport along networks of actin and microtubule cytoskeletal filaments. Perturbations to transport can significantly impact cellular viability and can result in disease at the organismal scale.
While much work in the past has focused on how motor properties affect transport, there has been growing interest in how the architecture and properties of the cytoskeletal network influences transport. Network features, characterized by the density, lengths, locations, orientations, and connectivity of filaments, as well as defects and blockades along them likely influences intracellular transport in much the same way that road connectivity and conditions are critical determinants of vehicular traffic.
At the level of a single filament, we explore how defects and traps can manifest themselves in anomalous transport properties. Interactions with the surroundings and the properties of the cargoes themselves are important considerations.
To understand transport at the network scale, we need to look beyond mean field treatments of ballistic transport and the actual architecture of the network is critical. We explore how, for example, particular filament arrangements can result in “traps” near the nucleus that result in highly variable transport times. Given such variability at both filament and network level transport, it seems likely that characteristics of the transport system such as cargo design and network architecture have been tuned in some cases to reduce variability, even at the expense of non-optimal mean transport times.
Below are some of our research papers on these topics:
"Cargo diffusion shortens single-kinesin runs at low viscous drag", John Wilson, David Quint, Ajay Gopinathan and Jing Xu, Scientific reports 9 (1), 4104
"Anomalous intracellular transport phases depend on cytoskeletal network features", Bryan Maelfeyt, S.M. Tabei, Ajay Gopinathan, Physical Review E 99 (6), 062404
"Membrane mediated motor kinetics in microtubule gliding assays", J Lopes, DA Quint, DE Chapman, M Xu, A Gopinathan, LS Hirst, Scientific reports 9 (1), 9584
"Multiple Kinesin-1 Motors Make for Faster Transport Through Dense Microtubule Networks", Joelle Labastide, David Quint, Reilly Curtin, Ajay Gopinathan, Jennifer Ross (submitted)
"Cargo diffusion shortens single-kinesin runs at low viscous drag", John Wilson, David Quint, Ajay Gopinathan and Jing Xu (submitted)
"Microtubule defects influence kinesin-based transport in vitro", Winnie Liang, K Faysal, Stephen King, Ajay Gopinathan, and Jing Xu, Biophysical Journal, 110, 10, 2229 (2016)
"Quantitative Determination of the Probability of Multiple-Motor Transport in Bead-Based Assays", Qiaochu Li, Stephen King, Ajay Gopinathan, and Jing Xu Biophysical Journal, 110, 12, 2720 (2016)
"Cytoskeletal network morphology regulates intracellular transport dynamics" , D. Ando, N. Korabel, K.C. Huang, A. Gopinathan, Biophysical Journal, 109(8), (2015) [cover article]
"Cooperative protofilament switching emerges from inter-motor interference in multiple-motor transport", D. Ando, M.K. Mattson, J. Xu, A. Gopinathan, Scientific reports, 4, 7255 (2014)
"Conformational changes, diffusion and collective behavior in monomeric kinesin based motility" K.C. Huang, C. Vega and Ajay Gopinathan, Journal of Physics: Condensed Matter, 23 (37), 374106 (2011)
While much work in the past has focused on how motor properties affect transport, there has been growing interest in how the architecture and properties of the cytoskeletal network influences transport. Network features, characterized by the density, lengths, locations, orientations, and connectivity of filaments, as well as defects and blockades along them likely influences intracellular transport in much the same way that road connectivity and conditions are critical determinants of vehicular traffic.
At the level of a single filament, we explore how defects and traps can manifest themselves in anomalous transport properties. Interactions with the surroundings and the properties of the cargoes themselves are important considerations.
To understand transport at the network scale, we need to look beyond mean field treatments of ballistic transport and the actual architecture of the network is critical. We explore how, for example, particular filament arrangements can result in “traps” near the nucleus that result in highly variable transport times. Given such variability at both filament and network level transport, it seems likely that characteristics of the transport system such as cargo design and network architecture have been tuned in some cases to reduce variability, even at the expense of non-optimal mean transport times.
Below are some of our research papers on these topics:
"Cargo diffusion shortens single-kinesin runs at low viscous drag", John Wilson, David Quint, Ajay Gopinathan and Jing Xu, Scientific reports 9 (1), 4104
"Anomalous intracellular transport phases depend on cytoskeletal network features", Bryan Maelfeyt, S.M. Tabei, Ajay Gopinathan, Physical Review E 99 (6), 062404
"Membrane mediated motor kinetics in microtubule gliding assays", J Lopes, DA Quint, DE Chapman, M Xu, A Gopinathan, LS Hirst, Scientific reports 9 (1), 9584
"Multiple Kinesin-1 Motors Make for Faster Transport Through Dense Microtubule Networks", Joelle Labastide, David Quint, Reilly Curtin, Ajay Gopinathan, Jennifer Ross (submitted)
"Cargo diffusion shortens single-kinesin runs at low viscous drag", John Wilson, David Quint, Ajay Gopinathan and Jing Xu (submitted)
"Microtubule defects influence kinesin-based transport in vitro", Winnie Liang, K Faysal, Stephen King, Ajay Gopinathan, and Jing Xu, Biophysical Journal, 110, 10, 2229 (2016)
"Quantitative Determination of the Probability of Multiple-Motor Transport in Bead-Based Assays", Qiaochu Li, Stephen King, Ajay Gopinathan, and Jing Xu Biophysical Journal, 110, 12, 2720 (2016)
"Cytoskeletal network morphology regulates intracellular transport dynamics" , D. Ando, N. Korabel, K.C. Huang, A. Gopinathan, Biophysical Journal, 109(8), (2015) [cover article]
"Cooperative protofilament switching emerges from inter-motor interference in multiple-motor transport", D. Ando, M.K. Mattson, J. Xu, A. Gopinathan, Scientific reports, 4, 7255 (2014)
"Conformational changes, diffusion and collective behavior in monomeric kinesin based motility" K.C. Huang, C. Vega and Ajay Gopinathan, Journal of Physics: Condensed Matter, 23 (37), 374106 (2011)