⇦Chinese Physics Letters, 2020, Vol. 37, No. 8, Article code 080103Views & Comments Strong Anisotropy of 3D Diffusion in Living Cells Xiaosong Chen (陈晓松)* Affiliations School of Systems Science, Beijing Normal University, Beijing 100875, China Received 20 July 2020; accepted 21 July 2020; published online 22 July 2020 *Corresponding author. Email: chenxs@bnu.edu.cn Citation Text: Chen X S 2020 Chin. Phys. Lett. 37 080103    Abstract DOI:10.1088/0256-307X/37/8/080103 PACS:01.10.-m, 87.15.A-, 87.16.Wd © 2020 Chinese Physics Society Article Text Starting from the never-ending agitated dance of pollen grains firstly discovered by Robert Brown in 1828, Brownian motion was known to represent the randomly diffusive movement of small particles in a simple solvent. Entering the twentieth century, milestone theories proposed by Albert Einstein,[1] Marian Smoluchowski,[2] and Paul Langevin[3] attributed Brownian motion to the irregular thermal movements of liquid molecules, bridging the gap between the macro-scale particle motion and the micro-scale molecule fluctuations. In their pioneering works, the particle random displacements exhibit a Gaussian probability distribution with the mean square displacement (MSD) increasing linearly in time. Further experimental verification was shortly achieved by Perrin in 1909.[4] Since then, the research on diffusion is unbroken both in experiment and theory, ranging from lifeless colloidal or polymeric solutions, to living biological systems.[5,6] In living cells, diffusion is crucial for molecule translocation in cytoplasm and mediates many important cellular processes.[7,8] With the advanced single-molecule imaging technique, tracking individual molecules or tracer particles in living cells offers us opportunities to directly investigate the intracellular diffusion, and to effectively probe the intracellular crowding and microscopic cytoarchitectures.[9,10] Different from Brownian motion, the anomalous diffusion, with a sublinear increase of MSD and a non-Gaussian distribution of displacement, was observed in cells.[11,12] It was also revealed that the diffusion is driven by not only thermal fluctuations but also the actively fluctuating forces in cells.[13] Although many studies have been made on intracellular diffusion in the past three decades, they were mainly carried out based on two-dimensional (2D) measurements, due to the lacking of sensitive instruments for measuring three-dimensional (3D) intracellular diffusion. In addition, an unverified assumption that the 3D diffusion in cells is isotropic is long-standing. However, the real 3D diffusion behavior of single molecules in cytoplasm as well as the 3D physical nature of cytoplasm are still unclear. Recently, Jiang et al.[14] discovered an anisotropical quasi-2D diffusion in cells by 3D single quantum dot (QD) tracking. They built a 3D single-particle tracking microscopy based on their previous 2D instrument,[10,15] achieving the lateral 27-nm ($x$- and $y$-directions) and axial 35-nm ($z$-direction) spatial resolutions, and millisecond temporal resolution at the single-molecule level. By using QDs as the fluorescence tracers and loading individual QDs into the cytoplasm of human cancer cells, they for the first time discovered a quasi-2D diffusion in living cells, with the axial motion being severely confined. Disrupting several cellular organelles does not alter the quasi-2D diffusion pattern, suggesting that the quasi-2D diffusion is robust and may be attributed to the complex and planar structures in the adherent cells. This study thus has revealed the uncovered 3D anisotropic diffusion and heterogeneous cytoarchitectures in cells. Another interesting suggestion in the work by Jiang et al.[14] is that cells may utilize the cytoarchitecture to control the intracellular diffusion dynamics and regulate macromolecule transport. The quasi-2D diffusion could effectively promote the translocation and shorten the searching time of biological molecules in adherent cells, which is reminiscent of the cell migration: fast lateral translocation of actin monomers is coupled with the flat spreading morphology of lamellipodia. With a broader perspective from 3D single-particle tracking, more investigations in cells are demanding to explore molecule behaviors, cytoarchitectures, and other physical natures in the real 3D intracellular world. These experiments would inspire related theoretical investigations of nonequilibrium complex systems. The interaction between experimental and theoretical studies in the future will reinforce our understanding about the diffusion inside living cells. References Über die von der molekularkinetischen Theorie der Wärme geforderte Bewegung von in ruhenden Flüssigkeiten suspendierten TeilchenZur kinetischen Theorie der Brownschen Molekularbewegung und der SuspensionenBrownian motion: a paradigm of soft matter and biological physicsIntroduction: 100years of Brownian motionInternational Review of CytologyMacromolecular Crowding and Confinement: Biochemical, Biophysical, and Potential Physiological ConsequencesStrange kinetics of single molecules in living cellsMapping Intracellular Diffusion Distribution Using Single Quantum Dot Tracking: Compartmentalized Diffusion Defined by Endoplasmic ReticulumAnomalous transport in the crowded world of biological cellsDynamic heterogeneity and non-Gaussian statistics for acetylcholine receptors on live cell membraneProbing the Stochastic, Motor-Driven Properties of the Cytoplasm Using Force Spectrum MicroscopyQuasi-Two-Dimensional Diffusion in Adherent Cells Revealed by Three-Dimensional Single Quantum Dot TrackingIntracellular transport is accelerated in early apoptotic cells
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