An efficient algorithm for extracting the magnitude of the measurement error for fractional dynamics.

Modern live-imaging fluorescent microscopy techniques following the stochastic motion of labeled tracer particles, i.e. single particle tracking (SPT) experiments, have uncovered significant deviations from the laws of Brownian motion in a variety of biological systems. Accurately characterizing the anomalous diffusion for SPT experiments has become a central issue in biophysics. However, measurement errors raise difficulty in the analysis of single trajectories. In this paper, we introduce a novel surface calibration method based on a fractionally integrated moving average (FIMA) process as an effective tool for extracting both the magnitude of the measurement error and the anomalous exponent for autocorrelated processes of various origins. This method is developed using a toy model - fractional Brownian motion disturbed by independent Gaussian white noise - and is illustrated on both simulated and experimental biological data. We also compare this new method with the mean-squared displacement (MSD) technique, extended to capture the measurement noise in the toy model, which shows inferior results. The introduced procedure is expected to allow for more accurate analysis of fractional anomalous diffusion trajectories with measurement errors across different experimental fields and without the need for any calibration measurements.

Loss of lamin A function increases chromatin dynamics in the nuclear interior.

Chromatin is organized in a highly ordered yet dynamic manner in the cell nucleus, but the principles governing this organization remain unclear. Similarly, it is unknown whether, and how, various proteins regulate chromatin motion and as a result influence nuclear organization. Here by studying the dynamics of different genomic regions in the nucleus of live cells, we show that the genome has highly constrained dynamics. Interestingly, depletion of lamin A strikingly alters genome dynamics, inducing a dramatic transition from slow anomalous diffusion to fast and normal diffusion. In contrast, depletion of LAP2α, a protein that interacts with lamin A and chromatin, has no such effect on genome dynamics. We speculate that chromosomal inter-chain interactions formed by lamin A throughout the nucleus contribute to chromatin dynamics, and suggest that the molecular regulation of chromatin diffusion by lamin A in the nuclear interior is critical for the maintenance of genome organization.

Ergodicity convergence test suggests telomere motion obeys fractional dynamics.

Anomalous diffusion, observed in many biological processes, is a generalized description of a wide variety of processes, all obeying the same law of mean-square displacement. Identifying the basic mechanisms of these observations is important for deducing the nature of the biophysical systems measured. We implement a previously suggested method for distinguishing between fractional Langevin dynamics, fractional Brownian motion, and continuous time random walk based on the ergodic nature of the data. We apply the method together with the recently suggested P-variation test and the displacement correlation to the lately measured dynamics of telomeres in the nucleus of mammalian cells and find strong evidence that the telomeres motion obeys fractional dynamics. The ergodic dynamics are observed experimentally to fit fractional Brownian or Langevin dynamics.

Transient anomalous diffusion of telomeres in the nucleus of mammalian cells.

We measured individual trajectories of fluorescently labeled telomeres in the nucleus of eukaryotic cells in the time range of 10(-2)-10(4)sec by combining a few acquisition methods. At short times the motion is subdiffusive with r2 approximately talpha and it changes to normal diffusion at longer times. The short times diffusion may be explained by the reptation model and the transient diffusion is consistent with a model of telomeres that are subject to a local binding mechanism with a wide but finite distribution of waiting times. These findings have important biological implications with respect to the genome organization in the nucleus.