257 research outputs found
Comment to the Paper of Michael J. Saxton: "A Biological Interpretation of Transient Anomalous Subdiffusion. I. Qualitative Model"
In a recent paper, Michael J. Saxton proposes to interpret as anomalous
diffusion the occurrence of apparent transient sub-diffusive regimes in
mean-squared displacements (MSD) plots, calculated from experimental
trajectories of molecules diffusing in living cells, acquired by Single
Particle (or Molecule) Tracking techniques (SPT or SMT). In this Comment,
without questioning the existence of sub-diffusive behaviors, which certainly
play a key role in numbers of mechanisms in living systems, we point out that
the data used by J.M. Saxton can as well be fitted by a simple law, resulting
from confined diffusion at short times, with a slower free diffusion
superimposed at larger times. When visualizing MSD plots, the transition from
short-term diffusion confined in domains of size L, to slower, longer-term free
diffusion, can be confused with anomalous diffusion over several orders of
magnitude of time.Comment: To appear in Biophysical Journa
Direct membrane proteinâDNA interactions required early in nuclear envelope assembly
Among the earliest events in postmitotic nuclear envelope (NE) assembly are the interactions between chromatin and the membranes that will fuse to form the NE
Probing microscopic origins of confined subdiffusion by first-passage observables
Subdiffusive motion of tracer particles in complex crowded environments, such
as biological cells, has been shown to be widepsread. This deviation from
brownian motion is usually characterized by a sublinear time dependence of the
mean square displacement (MSD). However, subdiffusive behavior can stem from
different microscopic scenarios, which can not be identified solely by the MSD
data. In this paper we present a theoretical framework which permits to
calculate analytically first-passage observables (mean first-passage times,
splitting probabilities and occupation times distributions) in disordered media
in any dimensions. This analysis is applied to two representative microscopic
models of subdiffusion: continuous-time random walks with heavy tailed waiting
times, and diffusion on fractals. Our results show that first-passage
observables provide tools to unambiguously discriminate between the two
possible microscopic scenarios of subdiffusion. Moreover we suggest experiments
based on first-passage observables which could help in determining the origin
of subdiffusion in complex media such as living cells, and discuss the
implications of anomalous transport to reaction kinetics in cells.Comment: 21 pages, 3 figures. Submitted versio
Quantitative analysis of single particle trajectories: mean maximal excursion method
An increasing number of experimental studies employ single particle tracking
to probe the physical environment in complex systems. We here propose and
discuss new methods to analyze the time series of the particle traces, in
particular, for subdiffusion phenomena. We discuss the statistical properties
of mean maximal excursions, i.e., the maximal distance covered by a test
particle up to time t. Compared to traditional methods focusing on the mean
squared displacement we show that the mean maximal excursion analysis performs
better in the determination of the anomalous diffusion exponent. We also
demonstrate that combination of regular moments with moments of the mean
maximal excursion method provides additional criteria to determine the exact
physical nature of the underlying stochastic subdiffusion processes. We put the
methods to test using experimental data as well as simulated time series from
different models for normal and anomalous dynamics, such as diffusion on
fractals, continuous time random walks, and fractional Brownian motion.Comment: 10 pages, 7 figures, 2 tables. NB: Supplementary material may be
found in the downloadable source file
The Chromosomal Passenger Complex Activates Polo Kinase at Centromeres
The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation
Anomalous versus slowed-down Brownian diffusion in the ligand-binding equilibrium
Measurements of protein motion in living cells and membranes consistently
report transient anomalous diffusion (subdiffusion) which converges back to a
Brownian motion with reduced diffusion coefficient at long times, after the
anomalous diffusion regime. Therefore, slowed-down Brownian motion could be
considered the macroscopic limit of transient anomalous diffusion. On the other
hand, membranes are also heterogeneous media in which Brownian motion may be
locally slowed-down due to variations in lipid composition. Here, we
investigate whether both situations lead to a similar behavior for the
reversible ligand-binding reaction in 2d. We compare the (long-time)
equilibrium properties obtained with transient anomalous diffusion due to
obstacle hindrance or power-law distributed residence times (continuous-time
random walks) to those obtained with space-dependent slowed-down Brownian
motion. Using theoretical arguments and Monte-Carlo simulations, we show that
those three scenarios have distinctive effects on the apparent affinity of the
reaction. While continuous-time random walks decrease the apparent affinity of
the reaction, locally slowed-down Brownian motion and local hinderance by
obstacles both improve it. However, only in the case of slowed-down Brownian
motion, the affinity is maximal when the slowdown is restricted to a subregion
of the available space. Hence, even at long times (equilibrium), these
processes are different and exhibit irreconcilable behaviors when the area
fraction of reduced mobility changes.Comment: Biophysical Journal (2013
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