Anomalous diffusion due to hindering by mobile obstacles undergoing Brownian motion or Orstein-Ulhenbeck processes.

In vivo measurements of the passive movements of biomolecules or vesicles in cells consistently report "anomalous diffusion," where mean-squared displacements scale as a power law of time with exponent α<1 (subdiffusion). While the detailed mechanisms causing such behaviors are not always elucidated, movement hindrance by obstacles is often invoked. However, our understanding of how hindered diffusion leads to subdiffusion is based on diffusion amidst randomly located immobile obstacles. Here, we have used Monte Carlo simulations to investigate transient subdiffusion due to mobile obstacles with various modes of mobility. Our simulations confirm that the anomalous regimes rapidly disappear when the obstacles move by Brownian motion. By contrast, mobile obstacles with more confined displacements, e.g., Orstein-Ulhenbeck motion, are shown to preserve subdiffusive regimes. The mean-squared displacement of tracked protein displays convincing power laws with anomalous exponent α that varies with the density of Orstein-Ulhenbeck (OU) obstacles or the relaxation time scale of the OU process. In particular, some of the values we observed are significantly below the universal value predicted for immobile obstacles in two dimensions. Therefore, our results show that subdiffusion due to mobile obstacles with OU type of motion may account for the large variation range exhibited by experimental measurements in living cells and may explain that some experimental estimates are below the universal value predicted for immobile obstacles.

[1]  A S Verkman,et al.  Molecular crowding reduces to a similar extent the diffusion of small solutes and macromolecules: measurement by fluorescence correlation spectroscopy , 2004, Journal of molecular recognition : JMR.

[2]  Petr Plechac,et al.  Microscopic simulation of membrane molecule diffusion on corralled membrane surfaces. , 2008, Biophysical journal.

[3]  October I Physical Review Letters , 2022 .

[4]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[5]  Erwin Frey,et al.  Critical dynamics of ballistic and Brownian particles in a heterogeneous environment. , 2007, The Journal of chemical physics.

[6]  Erwin Frey,et al.  Localization transition of the three-dimensional lorentz model and continuum percolation. , 2005, Physical review letters.

[7]  I. Tolic-Nørrelykke,et al.  Anomalous diffusion in living yeast cells. , 2004, Physical review letters.

[8]  J. Bouchaud,et al.  Anomalous diffusion in disordered media: Statistical mechanisms, models and physical applications , 1990 .

[9]  J. Klafter,et al.  First-passage times in complex scale-invariant media , 2007, Nature.

[10]  Erwin Frey,et al.  The localization transition of the two-dimensional Lorentz model , 2010, 1003.2918.

[11]  R Inman,et al.  Lateral diffusion of proteins in membranes. , 1987, Annual review of physiology.

[12]  G. Farquhar,et al.  Dependence of plastoquinol diffusion on the shape, size, and density of integral thylakoid proteins. , 2003, Biochimica et biophysica acta.

[13]  T. Franosch,et al.  Anomalous transport in the crowded world of biological cells , 2013, Reports on progress in physics. Physical Society.

[14]  Duccio Fanelli,et al.  Diffusion in a crowded environment. , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[15]  Mariella Dimiccoli,et al.  Localization of Protein Aggregation in Escherichia coli Is Governed by Diffusion and Nucleoid Macromolecular Crowding Effect , 2013, PLoS Comput. Biol..

[16]  D. Seigneurin [Cytometry]. , 2020, Annales de Pathologie.

[17]  Gillespie,et al.  Exact numerical simulation of the Ornstein-Uhlenbeck process and its integral. , 1996, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[18]  Paul R. Selvin,et al.  The role of microtubule movement in bidirectional organelle transport , 2008, Proceedings of the National Academy of Sciences.

[19]  Maggs,et al.  Subdiffusion and Anomalous Local Viscoelasticity in Actin Networks. , 1996, Physical review letters.

[20]  Anja Nenninger,et al.  Size Dependence of Protein Diffusion in the Cytoplasm of Escherichia coli , 2010, Journal of bacteriology.

[21]  M. Saxton,et al.  Lateral diffusion in a mixture of mobile and immobile particles. A Monte Carlo study. , 1990, Biophysical journal.

[22]  A. Kuznetsov,et al.  Intracellular transport of insulin granules is a subordinated random walk , 2013, Proceedings of the National Academy of Sciences.

[23]  Hugues Berry,et al.  Monte carlo simulations of enzyme reactions in two dimensions: fractal kinetics and spatial segregation. , 2002, Biophysical journal.

[24]  S. Vanapalli,et al.  Mapping of spatiotemporal heterogeneous particle dynamics in living cells. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[25]  A. Verkman,et al.  Crowding effects on diffusion in solutions and cells. , 2008, Annual review of biophysics.

[26]  J. Klafter,et al.  The random walk's guide to anomalous diffusion: a fractional dynamics approach , 2000 .

[27]  Jussi Timonen,et al.  Protein Diffusion in Mammalian Cell Cytoplasm , 2011, PloS one.

[28]  R. Cherry,et al.  Anomalous diffusion of major histocompatibility complex class I molecules on HeLa cells determined by single particle tracking. , 1999, Biophysical journal.

[29]  J. Theriot,et al.  Chromosomal Loci Move Subdiffusively through a Viscoelastic Cytoplasm , 2010 .

[30]  J Langowski,et al.  Anomalous diffusion of fluorescent probes inside living cell nuclei investigated by spatially-resolved fluorescence correlation spectroscopy. , 2000, Journal of molecular biology.

[31]  M. Weiss,et al.  Elucidating the origin of anomalous diffusion in crowded fluids. , 2009, Physical review letters.

[32]  J. Weisshaar,et al.  Subdiffraction-limit study of Kaede diffusion and spatial distribution in live Escherichia coli. , 2011, Biophysical journal.

[33]  T. Franosch,et al.  Cluster-resolved dynamic scaling theory and universal corrections for transport on percolating systems , 2008, 0811.1414.

[34]  M. Gell-Mann,et al.  Physics Today. , 1966, Applied optics.

[35]  Akihiro Kusumi,et al.  Phospholipids undergo hop diffusion in compartmentalized cell membrane , 2002, The Journal of cell biology.

[36]  Jason R. Swedlow,et al.  Cajal Body dynamics and association with chromatin are ATP-dependent , 2002, Nature Cell Biology.

[37]  Aubrey V. Weigel,et al.  Ergodic and nonergodic processes coexist in the plasma membrane as observed by single-molecule tracking , 2011, Proceedings of the National Academy of Sciences.

[38]  P. Heitjans,et al.  Diffusion in Condensed Matter , 2005 .

[39]  J. Langowski,et al.  Modeling diffusional transport in the interphase cell nucleus. , 2007, The Journal of chemical physics.

[40]  A. Caspi,et al.  Diffusion and directed motion in cellular transport. , 2002, Physical review. E, Statistical, nonlinear, and soft matter physics.

[41]  Yoshihisa Kubota,et al.  Multiple diffusion mechanisms due to nanostructuring in crowded environments. , 2007, Biophysical journal.

[42]  W. Webb,et al.  Constrained diffusion or immobile fraction on cell surfaces: a new interpretation. , 1996, Biophysical journal.

[43]  P. Argyrakis,et al.  Fractal to Euclidean crossover and scaling for random walkers on percolation clusters , 1984 .

[44]  R. Metzler,et al.  In vivo anomalous diffusion and weak ergodicity breaking of lipid granules. , 2010, Physical review letters.

[45]  E. Cox,et al.  Physical nature of bacterial cytoplasm. , 2006, Physical review letters.

[46]  Daniel S. Banks,et al.  Anomalous diffusion of proteins due to molecular crowding. , 2005, Biophysical journal.

[47]  Kevin Burrage,et al.  Sources of anomalous diffusion on cell membranes: a Monte Carlo study. , 2007, Biophysical journal.

[48]  J. Klafter,et al.  Probing microscopic origins of confined subdiffusion by first-passage observables , 2008, Proceedings of the National Academy of Sciences.

[49]  M. Hallek,et al.  Real-Time Single-Molecule Imaging of the Infection Pathway of an Adeno-Associated Virus , 2001, Science.

[50]  T. Franosch,et al.  Development of anomalous diffusion among crowding proteins , 2010, 1003.3748.

[51]  J. Elf,et al.  Single-molecule investigations of the stringent response machinery in living bacterial cells , 2011, Proceedings of the National Academy of Sciences.

[52]  R. Rosenfeld Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[53]  R. Metzler,et al.  Strange kinetics of single molecules in living cells , 2012 .

[54]  M. Elowitz,et al.  Protein Mobility in the Cytoplasm ofEscherichia coli , 1999, Journal of bacteriology.

[55]  P. Schwille,et al.  Near-critical fluctuations and cytoskeleton-assisted phase separation lead to subdiffusion in cell membranes. , 2010, Biophysical journal.

[56]  Gernot Guigas,et al.  The degree of macromolecular crowding in the cytoplasm and nucleoplasm of mammalian cells is conserved , 2007, FEBS letters.

[57]  Adrian H. Elcock,et al.  Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm , 2010, PLoS Comput. Biol..

[58]  M. Weiss,et al.  Anomalous subdiffusion is a measure for cytoplasmic crowding in living cells. , 2004, Biophysical journal.

[59]  J. Korlach,et al.  Fluorescence correlation spectroscopy with single-molecule sensitivity on cell and model membranes. , 1999, Cytometry.

[60]  M. Weiss,et al.  Probing the nanoscale viscoelasticity of intracellular fluids in living cells. , 2007, Biophysical journal.

[61]  M. Saxton Anomalous diffusion due to obstacles: a Monte Carlo study. , 1994, Biophysical journal.

[62]  W E Moerner,et al.  Translational diffusion of individual class II MHC membrane proteins in cells. , 2002, Biophysical journal.

[63]  S. Scheuring,et al.  Dynamics and diffusion in photosynthetic membranes from rhodospirillum photometricum. , 2006, Biophysical journal.

[64]  M. Longo,et al.  Anomalous subdiffusion in heterogeneous lipid bilayers , 2003 .

[65]  Y. Garini,et al.  Transient anomalous diffusion of telomeres in the nucleus of mammalian cells. , 2009, Physical review letters.

[66]  F. MacKintosh,et al.  Dynamic shear modulus of a semiflexible polymer network , 1998 .

[67]  Erwin Frey,et al.  Localization Transition of the 3D Lorentz Model and Continuum Percolation , 2005 .

[68]  Hédi Soula,et al.  Anomalous versus slowed-down Brownian diffusion in the ligand-binding equilibrium. , 2012, Biophysical journal.

[69]  Akihiro Kusumi,et al.  Ultrafine membrane compartments for molecular diffusion as revealed by single molecule techniques. , 2004, Biophysical journal.