New experimental techniques give a far more detailed picture of the motion of cellular components than was previously available. In single-particle tracking (SPT), computer-enhanced video microscopy is used to measure the 2d trajectories of labeled membrane proteins or lipids on the cell surface, and the 3d trajectories of proteins, nucleic acids, and various subcellular structures in the cytoplasm and nucleus. Typically the spatial resolution is tens of nanometers and the time resolution is tens of milliseconds. One of the major results of SPT is that a significant fraction of proteins and lipids in the plasma membrane undergo various types of non-Brownian motion, including anomalous subdiffusion, directed motion, and confined motion. Transitions are often observed between modes of motion. A similar picture is emerging for 3d motion within the cell. This project will use Monte Carlo computer simulation techniques and percolation theory to study heterogeneous motion in heterogeneous membranes, and its biological consequences. The work will examine various models of hindered diffusion, such as the effect of the screened electrostatic interaction of highly charged extracellular domains of membrane proteins. The effects of membrane heterogeneity on reaction kinetics will be studied, specifically the role of lipid rafts in cellular signal transduction. Simulations will be used to develop improved methods of SPT analysis for both the 2d and 3d cases. Other 3d work will model diffusion obstructed by the simplest geometric model of the cytoskeleton, and SPT of Cajal bodies in the nucleus.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Biophysical Chemistry Study Section (BBCB)
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Chin, Jean
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University of California Davis
Schools of Arts and Sciences
United States
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Saxton, Michael J (2014) Wanted: scalable tracers for diffusion measurements. J Phys Chem B 118:12805-17
Saxton, Michael J (2012) Wanted: a positive control for anomalous subdiffusion. Biophys J 103:2411-22
Saxton, Michael J (2010) Two-dimensional continuum percolation threshold for diffusing particles of nonzero radius. Biophys J 99:1490-9
Saxton, Michael J (2008) A biological interpretation of transient anomalous subdiffusion. II. Reaction kinetics. Biophys J 94:760-71
Saxton, Michael J (2007) A biological interpretation of transient anomalous subdiffusion. I. Qualitative model. Biophys J 92:1178-91
Saxton, Michael J (2007) Modeling 2D and 3D diffusion. Methods Mol Biol 400:295-321
Deverall, M A; Gindl, E; Sinner, E-K et al. (2005) Membrane lateral mobility obstructed by polymer-tethered lipids studied at the single molecule level. Biophys J 88:1875-86
Ng, Yuen-Keng; Lu, Xinghua; Gulacsi, Alexandra et al. (2003) Unexpected mobility variation among individual secretory vesicles produces an apparent refractory neuropeptide pool. Biophys J 84:4127-34
Saxton, M J (2001) Anomalous subdiffusion in fluorescence photobleaching recovery: a Monte Carlo study. Biophys J 81:2226-40
Saxton, M J (1997) Single-particle tracking: the distribution of diffusion coefficients. Biophys J 72:1744-53

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