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Sources of Anomalous Diffusion on Cell Membranes: A Monte Carlo Study

Dan V. Nicolau, Jr. ^*, John F. Hancock  and Kevin Burrage ^*

^* Advanced Computational Modelling Centre, Department of Mathematics, and Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia

Correspondence: Address reprint requests to Kevin Burrage, Advanced Computational Modelling Centre, University of Queensland, St Lucia 4072. E-mail: kb{at}maths.uq.edu.au; or John Hancock, Institute for Molecular Bioscience, University of Queensland, St Lucia 4072, Australia. E-mail: j.hancock{at}imb.uq.edu.au.

A stochastic random walk model of protein molecule diffusion on a cell membrane was used to investigate the fundamental causes of anomalous diffusion in two-dimensional biological media. Three different interactions were considered: collisions with fixed obstacles, picket fence posts, and capture by, or exclusion from, lipid rafts. If motion is impeded by randomly placed, fixed obstacles, we find that diffusion can be highly anomalous, in agreement with previous studies. In contrast, collision with picket fence posts has a negligible effect on the anomalous exponent at realistic picket fence parameters. The effects of lipid rafts are more complex. If proteins partition into lipid rafts there is a small to moderate effect on the anomalous exponent, whereas if proteins are excluded from rafts there is a large effect on the anomalous exponent. In combination, these mechanisms can explain the level of anomaly in experimentally observed membrane diffusion, suggesting that anomalous diffusion is caused by multiple mechanisms whose effects are approximately additive. Finally, we show that the long-range diffusion rate, D_macro, estimated from fluorescence recovery after photobleaching studies, can be much smaller than D_micro, the small-scale diffusion rate, and is highly sensitive to obstacle densities and other impeding structures.

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