Inferring diffusion in single live cells at the single molecule level

The movement of molecules inside living cells is a fundamental feature of biological processes. The ability to both observe and analyse the details of molecular diffusion in vivo at the single molecule and single cell level can add significant insight into understanding molecular architectures of diffusing molecules and the nanoscale environment in which the molecules diffuse. The tool of choice for monitoring dynamic molecular localization in live cells is fluorescence microscopy, especially so combining total internal reflection fluorescence (TIRF) with the use of fluorescent protein (FP) reporters in offering exceptional imaging contrast for dynamic processes in the cell membrane under relatively physiological conditions compared to competing single molecule techniques. There exist several different complex modes of diffusion, and discriminating these from each other is challenging at the molecular level due to underlying stochastic behaviour. Analysis is traditionally performed using mean square displacements of tracked particles, however, this generally requires more data points than is typical for single FP tracks due to photophysical instability. Presented here is a novel approach allowing robust Bayesian ranking of diffusion processes (BARD) to discriminate multiple complex modes probabilistically. It is a computational approach which biologists can use to understand single molecule features in live cells.Comment: combined ms (1-37 pages, 8 figures) and SI (38-55, 3 figures

Dynamical response of a pinned two-dimensional Wigner crystal

We re-examine a long-standing problem of a finite-frequency conductivity of a weakly pinned two-dimensional classical Wigner crystal. In this system an inhomogeneously broadened absorption line (pinning mode) centered at disorder and magnetic field dependent frequency $\omega_p$ is known to appear. We show that the relative linewidth $\Delta \omega_p / \omega_p$ of the pinning mode is of the order of one in weak magnetic fields, exhibits a power-law decrease in intermediate fields, and eventually saturates at a small value in strong magnetic fields. The linewidth narrowing is due to a peculiar mechanism of mixing between the stiffer longitudinal and the softer transverse components of the collective excitations. The width of the high-field resonance proves to be related to the density of states in the low-frequency tail of the zero-field phonon spectrum. We find a qualitative agreement with recent experiments and point out differences from the previous theoretical work on the subject.Comment: 19 pages, 11 figures. Supersedes cond-mat/990424

On the Large RR-charge Expansion in N=2{\mathcal N} = 2 Superconformal Field Theories

In this note we study two point functions of Coulomb branch chiral ring elements with large $R$-charge, in quantum field theories with ${\mathcal N} = 2$ superconformal symmetry in four spacetime dimensions. Focusing on the case of one-dimensional Coulomb branch, we use the effective-field-theoretic methods of arXiv:1706.05743, to estimate the two-point function $${\mathcal Y}_n \equiv |x-y|^{2n\Delta_{\mathcal O}}\left<({\mathcal O}(x))^n(\bar{\mathcal O}(y))^n\right>$$ in the limit where the operator insertion On has large total $R$-charge ${\mathcal J} = n\Delta_{\mathcal O}$. We show that ${\mathcal Y}_n$ has a nontrivial but universal asymptotic expansion at large ${\mathcal J}$, of the form $${\mathcal Y}_n = {\mathcal J}! \left(\frac{\left| {\mathbf N}_{\mathcal O}\right|}{2\pi}\right)^{2{\mathcal J}}{\mathcal J}^\alpha {\tilde{\mathcal Y}}_n$$ where ${\mathcal Y}_n$ approaches a constant as $n\to\infty$, and ${\mathbf N}_{\mathcal O}$ is an $n$-independent constant describing on the normalization of the operator relative to the effective Abelian gauge coupling. The exponent $\alpha$ is a positive number proportional to the difference between the $a$-anomaly coefficient of the underlying CFT and that of the effective theory of the Coulomb branch. For Lagrangian SCFT, we check our predictions against exact results from supersymmetric localization of Baggio et. al. and Gerchkovitz et. al., and find precise agreement for the logarithm ${\mathcal B}_n = \log{\mathcal Y}_n$, up to and including order $\log{\mathcal J}$. We also give predictions for the growth of two-point functions in all rank-one SCFT in the classification of Argyres et. al. In this way, we show the large-$R$-charge expansion serves as a bridge from the world of unbroken superconformal symmetry, OPE data, and bootstraps, to the world of the low-energy dynamics of the moduli space of vacua.Comment: minor change

Onset of many-body chaos in the O(N)O(N) model

The growth of commutators of initially commuting local operators diagnoses the onset of chaos in quantum many-body systems. We compute such commutators of local field operators with $N$ components in the $(2+1)$-dimensional $O(N)$ nonlinear sigma model to leading order in $1/N$. The system is taken to be in thermal equilibrium at a temperature $T$ above the zero temperature quantum critical point separating the symmetry broken and unbroken phases. The commutator grows exponentially in time with a rate denoted $\lambda_L$. At large $N$ the growth of chaos as measured by $\lambda_L$ is slow because the model is weakly interacting, and we find $\lambda_L \approx 3.2 T/N$. The scaling with temperature is dictated by conformal invariance of the underlying quantum critical point. We also show that operators grow ballistically in space with a "butterfly velocity" given by $v_B/c \approx 1$ where $c$ is the Lorentz-invariant speed of particle excitations in the system. We briefly comment on the behavior of $\lambda_L$ and $v_B$ in the neighboring symmetry broken and unbroken phases.Comment: (1+55) pages, 13 figures; (v2) Final published versio

Anomalous transport in the crowded world of biological cells

A ubiquitous observation in cell biology is that diffusion of macromolecules and organelles is anomalous, and a description simply based on the conventional diffusion equation with diffusion constants measured in dilute solution fails. This is commonly attributed to macromolecular crowding in the interior of cells and in cellular membranes, summarising their densely packed and heterogeneous structures. The most familiar phenomenon is a power-law increase of the MSD, but there are other manifestations like strongly reduced and time-dependent diffusion coefficients, persistent correlations, non-gaussian distributions of the displacements, heterogeneous diffusion, and immobile particles. After a general introduction to the statistical description of slow, anomalous transport, we summarise some widely used theoretical models: gaussian models like FBM and Langevin equations for visco-elastic media, the CTRW model, and the Lorentz model describing obstructed transport in a heterogeneous environment. Emphasis is put on the spatio-temporal properties of the transport in terms of 2-point correlation functions, dynamic scaling behaviour, and how the models are distinguished by their propagators even for identical MSDs. Then, we review the theory underlying common experimental techniques in the presence of anomalous transport: single-particle tracking, FCS, and FRAP. We report on the large body of recent experimental evidence for anomalous transport in crowded biological media: in cyto- and nucleoplasm as well as in cellular membranes, complemented by in vitro experiments where model systems mimic physiological crowding conditions. Finally, computer simulations play an important role in testing the theoretical models and corroborating the experimental findings. The review is completed by a synthesis of the theoretical and experimental progress identifying open questions for future investigation.Comment: review article, to appear in Rep. Prog. Phy

Localization and chiral symmetry in 2+1 flavor domain wall QCD

We present results for the dependence of the residual mass of domain wall fermions (DWF) on the size of the fifth dimension and its relation to the density and localization properties of low-lying eigenvectors of the corresponding hermitian Wilson Dirac operator relevant to simulations of 2+1 flavor domain wall QCD. Using the DBW2 and Iwasaki gauge actions, we generate ensembles of configurations with a $16^3\times 32$ space-time volume and an extent of 8 in the fifth dimension for the sea quarks. We demonstrate the existence of a regime where the degree of locality, the size of chiral symmetry breaking and the rate of topology change can be acceptable for inverse lattice spacings $a^{-1} \ge 1.6$ GeV.Comment: 59 Pages, 23 figures, 1 MPG linke