Bulletin of the American Physical Society
APS March Meeting 2019
Volume 64, Number 2
Monday–Friday, March 4–8, 2019; Boston, Massachusetts
Session R64: Physics of Intracellular TransportFocus
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Sponsoring Units: DBIO Chair: Jing Xu, Univ of California - Merced Room: BCEC 259B |
Thursday, March 7, 2019 8:00AM - 8:36AM |
R64.00001: The complexity of microtubule-based motility Invited Speaker: Michael Vershinin The tug of war between multiple molecular motors driving the same cargo can take many forms and result in many observable motility phenotypes. I will discuss some of the relevant cases, from movement across microtubule intersections to a minimal tug of war system on a single microtubule. I will show that the overall range of behaviors is remarkable large and in particular that cargos can remain in a tug of war state for extremely long times and that this has significant implications for both cargo routing in cells and for our ability to tell tug of war processes from other pathways to immotility such as diffusion. Finally, I will discuss viable approaches for identifying tug of war in biological systems. |
Thursday, March 7, 2019 8:36AM - 9:12AM |
R64.00002: Macromolecular crowding regulates the velocity of intracellular transport by kinesin-1 motors Invited Speaker: George Shubeita The cytosol is crowded with a high concentration of macromolecules. Crowding can alter protein conformation, binding rates, and reaction kinetics, yet it is not known how crowding affects intracellular cargo transport by molecular motor proteins. We use live cell and single-molecule imaging and optical trap measurements to uncover the consequences of macromolecular crowding on cargo transport by kinesin-1 motors. Surprisingly, we find that crowding significantly slows transport by teams of motors, while having no effect on single motor velocity. We find that this emergent property of kinesin teams results from the individuals’ increased sensitivity to hindering load in a crowded medium. Our results highlight the importance of motor-motor interactions in cargo transport, explain the long observed variability of cargo velocity, and suggest the use of crowding as a control parameter to study kinesin’s mechanochemical cycle. |
Thursday, March 7, 2019 9:12AM - 9:24AM |
R64.00003: Intracellular transport is accelerated in early apoptotic cells Hui Li Apoptosis is a process of programmed cell death with dramatic changes in cell morphology and organization, during which signaling molecules are transported within the cells between different organelles. However, how the intracellular transport changes in cells undergoing apoptosis remains unknown. Here, we study the dynamics of intracellular transport by using single-particle tracking method, and find that both the directed motion and diffusive motion of endocytic vesicles are accelerated in early apoptotic cells. With careful elimination of the other factors involving in the intracellular transport, the reason for the acceleration is attributed to be the elevation of ATP concentration. More importantly, we show that the accelerated intracellular transport is critical for apoptosis. Apoptosis is delayed when the dynamics of intracellular transport is regulated back to the normal level. Our results demonstrate the important role of transport dynamics in apoptosis and shed light on the apoptosis mechanism from a physical perspective. |
Thursday, March 7, 2019 9:24AM - 9:36AM |
R64.00004: Doppler Spectroscopy of Intracellular Motion in Revived Flash-Frozen Cancer Tissues Zhen Hua, Zhe Li, John Turek, Micheal Childress, David Nolte Biodynamic imaging is a high-content optical imaging technology based on Doppler spectroscopy and digital holography that uses dynamic speckle as high-content image contrast to probe living tissue. The multimode mixing of Doppler signals produces a fluctuation spectrum that is a function of the acquisition time relative to the persistence time of intracellular transport and hence provides a measure of cellular activity. Creating Doppler spectrograms of tumor tissues responding to anticancer agents usually relies on patient enrollment in IRB-approved trials, which is slow and inefficient. However, if flash-frozen biopsies could be revived and measured, then a large reservoir of tissue-banked samples could become available for phenotypic library building. We have performed biodynamic imaging measurements of flash-frozen canine B-cell cancer tissue and compared the drug-response spectrograms to results from fresh tissues from the same dogs. By compensating for tissue trauma in the frozen sample, we demonstrate a high accuracy for patient clustering between the fresh and frozen samples when correlating with clinical outcomes, identifying resistance or sensitivity to their prescribed chemotherapy. |
Thursday, March 7, 2019 9:36AM - 9:48AM |
R64.00005: A model of diffusion through a potential captures the effect of competition on the efficiency and speed of nucleocytoplasmic transport Tiantian Zheng, Anton Zilman The nuclear pore complex (NPC) facilitates the selective transport of materials between the nucleus and cytoplasm in eukaryotic cells. Typically, many cargo are simultaneously present within the NPC during transport, and it is not fully understood how the NPC can function efficiently despite the crowding in the channel. In this study, we simulate transport through an NPC-like channel with coarse-grained cargoes and NPC-associated intrinsically disordered proteins (FG nucleoporins). From the results of this simulation, we show that cargo densities and trajectories along the direction of transport can be captured by a model of 1-dimensional diffusion through a potential, which is an effective potential arising through the interactions between cargoes and NPC components, and is modified by the non-equilibrium density profiles of cargoes inside the channel. With this framework, we are able to account qualitatively for previously unexplained experimental data which show that an increased number of cargo results in both increased efficiency and speed of transport. Our model therefore provides an explanation for why crowding does not necessarily affect the functioning of the NPC in a negative way, which can explain how the NPC can achieve both high specificity and high throughput. |
Thursday, March 7, 2019 9:48AM - 10:00AM |
R64.00006: A Semi-Analytical Model to Investigate Cargo Transport by Bi-Directional Molecular Motor Ensemble Rachit Shrivastava, Shreyas Bhaban, James Melbourne, Sivaraman Rajaganapathy, Murti Salapaka Deciphering mechanism of transportation of organelles by molecular motors is crucial to understand the genesis of neurodegenerative diseases. We model the ensemble behavior of motors using a semi-analytical approach. This approach uses an individual motor’s model to predict their ensemble behavior. The process of cargo transportation is modeled as Markov process with molecular motor arrangements being as its state which satisfies Markov property. Exact probabilities distribution functions of the relative configurations of motor is determined in order decipher the cargo transportation process. |
Thursday, March 7, 2019 10:00AM - 10:12AM |
R64.00007: Two-Species Active Transport along Cylindrical Biofilaments is Limited by Emergent Topological Hindrance Patrick Wilke, Emanuel Reithmann, Erwin Frey Motivated by recent experimental studies that have addressed the stepping behavior of kinesins, we investigate a lattice gas model for simultaneous transport of two species of active particles on a cylinder. The species are distinguished by their different gaits: While the first species moves straight ahead, the second follows a helical path. We show that the collective properties of such systems critically differ from those of one-species transport. This is most evident in a jamming transition far below full occupation, as well as in nonequilibrium pattern formation. The altered behavior arises because—unlike the case in single-species transport—any given position may be targeted by two particles from different directions at the same time. However, a particle can leave a given position only in one direction. This simple change in connectivity significantly amplifies the impact of steric interactions and thus becomes a key determinant of mixed species transport. We computationally characterize this type of hindrance and develop a comprehensive theory for collective two-species transport along a cylinder. Our observations show high robustness against model extensions that account for additional biomolecular features which suggests relevance also in a biological context. |
Thursday, March 7, 2019 10:12AM - 10:24AM |
R64.00008: Simulation of membrane-bound cargo transport by teams of kinesin motors Niranjan Sarpangala, Ajay Gopinathan In eukaryotic cells, membrane-bound cargoes are transported by teams of molecular motors. Motors on such cargoes diffuse on the lipid membrane. How the fluidity of the membrane affects transport characteristics is still not well understood. Here we develop a stochastic dynamical simulation of kinesin-based cargo transport along microtubules that explicitly considers the Langevin dynamics of motors on the surface of cargo. We study how the number of bound motors, run length, the velocity of cargo and binding rates are influenced by parameters like the diffusion coefficient of motors on cargo surface, ATP concentration, and the cargo size. We show that the distribution of free motors on microtubule-bound cargo surface depends on these parameters and affects the rebinding of cargo to microtubule after its detachment, thus affecting overall transport. Our work suggests that the consideration of motor diffusivity should be important in the cellular context. |
Thursday, March 7, 2019 10:24AM - 10:36AM |
R64.00009: Modeling non-processive molecular motors on multiple cytoskeletal filaments Naruemon Rueangkham Molecular motors stepping along cytoskeletal filaments facilitate intracellular transport and organelle positioning. Molecular motors can work either alone or cooperatively. They are often classified according to their processivity. Processive motors never unbind from the filaments during transporting whereas non-processive motors unbind from the filaments frequently. In this work, we study the collective behaviors of N processive and non-processive molecular motors stepping along one and multiple microtubule filaments in stochastic simulations using Monte Carlo methods. The motor dynamics follow biased random walks subjected to a simple exclusion process. We consider the analytical solution of velocity (V) of a collection of N processive and non-processive motors along one filament as a function of applied force (F). We compare these analytical solutions to our stochastic simulation results. We also show the simulation results of F-V relations of non-processive motors stepping along and switching between multiple filaments. In this case, the applied load is shared between the leading motors on each filament. |
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