Signal Processing during Developmental Multicellular Patterning

Developing design strategies for tissue engineering and regenerative medicine is limited by our nascent understanding of how cell populations self-organize into multicellular structures on synthetic scaffolds. Mechanistic insights can be gleaned from the quantitative analysis of biomolecular signals that drive multicellular patterning during the natural processes of embryonic and adult development. This review describes three critical layers of signal processing that govern multicellular patterning: spatiotemporal presentation of extracellular cues, intracellular signaling networks that mediate crosstalk among extracellular cues, and finally, intranuclear signal integration at the level of transcriptional regulation. At every level in this hierarchy, the quantitative attributes of signals have a profound impact on patterning. We discuss how experiments and mathematical models are being used to uncover these quantitative features and their impact on multicellular phenotype

The influence of receptor-mediated interactions on reaction-diffusion mechanisms of cellular self-organisation

Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction

L-selectin mediated leukocyte tethering in shear flow is controlled by multiple contacts and cytoskeletal anchorage facilitating fast rebinding events

L-selectin mediated tethers result in leukocyte rolling only above a threshold in shear. Here we present biophysical modeling based on recently published data from flow chamber experiments (Dwir et al., J. Cell Biol. 163: 649-659, 2003) which supports the interpretation that L-selectin mediated tethers below the shear threshold correspond to single L-selectin carbohydrate bonds dissociating on the time scale of milliseconds, whereas L-selectin mediated tethers above the shear threshold are stabilized by multiple bonds and fast rebinding of broken bonds, resulting in tether lifetimes on the timescale of $10^{-1}$ seconds. Our calculations for cluster dissociation suggest that the single molecule rebinding rate is of the order of $10^4$ Hz. A similar estimate results if increased tether dissociation for tail-truncated L-selectin mutants above the shear threshold is modeled as diffusive escape of single receptors from the rebinding region due to increased mobility. Using computer simulations, we show that our model yields first order dissociation kinetics and exponential dependence of tether dissociation rates on shear stress. Our results suggest that multiple contacts, cytoskeletal anchorage of L-selectin and local rebinding of ligand play important roles in L-selectin tether stabilization and progression of tethers into persistent rolling on endothelial surfaces.Comment: 9 pages, Revtex, 4 Postscript figures include

Long-Range Exciton Diffusion in Two-Dimensional Assemblies of Cesium Lead Bromide Perovskite Nanocrystals

F\"orster Resonant Energy Transfer (FRET)-mediated exciton diffusion through artificial nanoscale building block assemblies could be used as a new optoelectronic design element to transport energy. However, so far nanocrystal (NC) systems supported only diffusion length of 30 nm, which are too small to be useful in devices. Here, we demonstrate a FRET-mediated exciton diffusion length of 200 nm with 0.5 cm2/s diffusivity through an ordered, two-dimensional assembly of cesium lead bromide perovskite nanocrystals (PNC). Exciton diffusion was directly measured via steady-state and time-resolved photoluminescence (PL) microscopy, with physical modeling providing deeper insight into the transport process. This exceptionally efficient exciton transport is facilitated by PNCs high PL quantum yield, large absorption cross-section, and high polarizability, together with minimal energetic and geometric disorder of the assembly. This FRET-mediated exciton diffusion length matches perovskites optical absorption depth, opening the possibility to design new optoelectronic device architectures with improved performances, and providing insight into the high conversion efficiencies of PNC-based optoelectronic devices

Correlated Exciton Transport in Rydberg-Dressed-Atom Spin Chains

We investigate the transport of excitations through a chain of atoms with non-local dissipation introduced through coupling to additional short-lived states. The system is described by an effective spin-1/2 model where the ratio of the exchange interaction strength to the reservoir coupling strength determines the type of transport, including coherent exciton motion, incoherent hopping and a regime in which an emergent length scale leads to a preferred hopping distance far beyond nearest neighbors. For multiple impurities, the dissipation gives rise to strong nearest-neighbor correlations and entanglement. These results highlight the importance of non-trivial dissipation, correlations and many-body effects in recent experiments on the dipole-mediated transport of Rydberg excitations.Comment: 5 page

The effects of polydispersity and metastability on crystal growth kinetics

We investigate the effect of metastable gas-liquid (G-L) separation on crystal growth in a system of either monodisperse or slightly size-polydisperse square well particles, using a simulation setup that allows us to focus on the growth of a single crystal. Our system parameters are such that, inside the metastable G-L binodal, a macroscopic layer of the gas phase "coats" the crystal as it grows, consistent with experiment and theoretical free energy considerations. Crucially, the effect of this metastable G-L separation on the crystal growth rate depends qualitatively on whether the system is polydisperse. We measure reduced polydispersity and qualitatively different local size ordering in the crystal relative to the fluid, proposing that the required fractionation is dynamically facilitated by the gas layer. Our results show that polydispersity and metastability, both ubiquitous in soft matter, must be considered in tandem if their dynamical effects are to be understood.Comment: Published in Soft Matter. DOI: 10.1039/C3SM27627

Simulation of nanostructure-based high-efficiency solar cells: challenges, existing approaches and future directions

Many advanced concepts for high-efficiency photovoltaic devices exploit the peculiar optoelectronic properties of semiconductor nanostructures such as quantum wells, wires and dots. While the optics of such devices is only modestly affected due to the small size of the structures, the optical transitions and electronic transport can strongly deviate from the simple bulk picture known from conventional solar cell devices. This review article discusses the challenges for an adequate theoretical description of the photovoltaic device operation arising from the introduction of nanostructure absorber and/or conductor components and gives an overview of existing device simulation approaches.Comment: Invited paper, accepted for publication in IEEE Journal of Selected Topics in Quantum Electronic

The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel