Heterogeneities Shape Passive Intracellular Transport

Abstract

A living cell's interior is one of the most complex and intrinsically dynamic systems, providing an elaborate interplay between cytosolic crowding and ATP-driven motion that controls cellular functionality. Here, we investigated two distinct fundamental features of the merely passive, non-biomotor-shuttled material transport within the cytoplasm of Dictyostelium discoideum cells: the anomalous non-linear scaling of the mean-squared displacement of a 150-nm-diameter particle and non-Gaussian distribution of increments. Relying on single-particle tracking data of 320,000 data points, we performed a systematic analysis of four possible origins for non-Gaussian transport: 1) sample-based variability, 2) rarely occurring strong motion events, 3) ergodicity breaking/aging, and 4) spatiotemporal heterogeneities of the intracellular medium. After excluding the first three reasons, we investigated the remaining hypothesis of a heterogeneous cytoplasm as cause for non-Gaussian transport. A, to our knowledge, novel fit model with randomly distributed diffusivities implementing medium heterogeneities suits the experimental data. Strikingly, the non-Gaussian feature is independent of the cytoskeleton condition and lag time. This reveals that efficiency and consistency of passive intracellular transport and the related anomalous scaling of the mean-squared displacement are regulated by cytoskeleton components, whereas cytoplasmic heterogeneities are responsible for the generic, non-Gaussian distribution of increments.

Diffusion-influenced reaction rates in the presence of pair interactions

“…Eventually, the reaction frequency is obtained by matching inner and outer solutions for the concentration, Eq. (16). Employing the numerical value for ′ ( ) and our previous result, Eq.…”

Large Deviations for Continuous Time Random Walks

“…However, in Reference [ 4 ] Chaudhuri, Berthier, and Kob, discovered what might turn out to be a no less universal feature of random walks. Analyzing experimental and numerical data, e.g., the motion of particles in glass forming systems, they revealed an exponential decay of the packet of spreading particles; see related works in References [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Soon after this, a similar behavior described by the Laplace distribution, was found for many other systems, including for molecules in the cell environment [ 7 , 26 , 27 ].…”

Subtle changes in crosslinking drive diverse anomalous transport characteristics in actin-microtubule networks

“…Numerous crosslinking proteins that can link actin to actin 4-7 , microtubules to microtubules [8][9][10] , and actin to microtubules [11][12][13][14][15] enable the cytoskeleton to adopt diverse architectures and stiffnesses to drive key processes such as cell motility, meiosis and apoptosis 10,[16][17][18] . These varying structural and rheological properties, in turn, directly impact the intracellular transport of vesicles and macromolecules traversing the cytoplasm 14,15,19,20 . More generally, thermal transport of particles in biomimetic, cell-like and crowded environments continues to be intensely investigated due to the intriguing anomalous properties, i.e.…”

“…More generally, thermal transport of particles in biomimetic, cell-like and crowded environments continues to be intensely investigated due to the intriguing anomalous properties, i.e. properties not found in normal Brownian motion 14,15,[19][20][21][22][23][24] , that have been reported in these systems.…”