Core Polarity Research Articles

Constitutive activation of β-catenin in odontoblasts induces aberrant pulp calcification in mouse incisors.

During dentin formation, odontoblast polarization ensures that odontoblasts directionally secrete dentin matrix protein, leading to tubular dentin formation; however, little is known about the major features and regulatory mechanisms of odontoblast polarization. In a study of epithelial cell polarization, β-catenin was shown to serve as a structural component of cadherin-based adherens junctions to initiate cell polarity. However, the role of β-catenin in odontoblast polarization has not been well investigated. In this study, we explored whether β-catenin participated in odontoblast polarization to regulate the secretion of mineralization proteins. We established Col1-CreErt2; β-catenin exon3fl/fl (CA-β-catenin) mice, which constitutively activate β-catenin in odontoblasts. CA-β-catenin mice exhibited disorganization and depolarization of incisor odontoblasts. Moreover, the incisor dentin was hypomineralized, and ectopic calcification was found in mouse incisor pulp. In addition, by constitutive activation of β-catenin, the expression levels of the core polarity molecule Cdc42 and its downstream polarity protein complex Par3-Par6-aPKC were decreased in the incisors of CA-β-catenin mice. These findings suggest that β-catenin plays an essential role in dentin formation by regulating odontoblast polarization.

Four different mechanisms for switching cell polarity.

The mechanisms and design principles of regulatory systems establishing stable polarized protein patterns within cells are well studied. However, cells can also dynamically control their cell polarity. Here, we ask how an upstream signaling system can switch the orientation of a polarized pattern. We use a mathematical model of a core polarity system based on three proteins as the basis to study different mechanisms of signal-induced polarity switching. The analysis of this model reveals four general classes of switching mechanisms with qualitatively distinct behaviors: the transient oscillator switch, the reset switch, the prime-release switch, and the push switch. Each of these regulatory mechanisms effectively implements the function of a spatial toggle switch, however with different characteristics in their nonlinear and stochastic dynamics. We identify these characteristics and also discuss experimental signatures of each type of switching mechanism.

Periodic vortex core switching in curved magnetic nanodisk

Periodic switching of magnetic vortex core driven by alternative magnetic field, applied perpendicularly, is investigated in a curved permalloy nanodisk by using micromagnetic simulation. Modulated by the curvature, the oscillations of the out-of-plane magnetization, caused by the external magnetic field, are confined in the center region, closed to the core, which reduces the threshold switching field down to 3 mT. While, the excitation of radial spin waves after a core switching dominates the reversal process generally in flat nanodisks, making it hard to control the final core polarity. The released spin waves in the center region during the core switching are relatively weak in curved nanodisk with most of radial spin waves dissipated to the thick edge part, resulting in a stable periodic vortex core switching.

Dynamical switching of confined magnetic skyrmions under circular magnetic fields

Understanding the dynamical properties of magnetic skyrmions is of prime importance for realization of skyrmion based devices. Here we report on the dynamics of a confined magnetic skyrmion under application of circular magnetic fields (CMFs). We provide the complex map of the dynamical states and demonstrate that under some conditions CMFs can change the skyrmion number and lead to the switching of the core polarity. Combing the results of micromagnetic simulations with those of analytical calculations, based on the extended Thiele equation, we unravel the physical mechanism behind this dynamical switching. The core switching is associated with the dynamical motions of the skyrmion driven by a CMF. The formation of domain walls and their movement from the border towards the center leads to shrinking of the skyrmion and the creation of a skyrmion with opposite core polarity. The results provide a guideline for checking the skyrmion's stability as well as an efficient way for switching the core polarity using CMFs.

Genetic alterations of epithelial polarity genes are associated with loss of polarity in invasive breast cancer

Breast cancer remains a leading cause of cancer-related death for women. The stepwise development of breast cancer through preinvasive to invasive disease is associated with progressive disruption of cellular and tissue organization. Apical-basal polarity is thought to be a barrier to breast cancer development, but the extent and potential mechanisms that contribute to disrupted polarity are incompletely understood. To investigate the cell polarity status of invasive breast cancers, we performed multiplex imaging of polarity markers on tissue cores from 432 patients from a spectrum of grades, stages and molecular subtypes. Apical-basal cell polarity was lost in 100% of cells in all cases studied, indicating that loss of epithelial polarity may be a universal feature of invasive breast cancer. We then analyzed genomic events from the TCGA dataset for an 18-gene set of core polarity genes. Coamplification of polarity genes with established breast oncogenes was found, which is consistent with functional cooperation within signaling amplicons. Gene-expression levels of several polarity genes were significantly associated with survival, and protein localization of Par6 correlated with higher grade, nodal metastasis and molecular subtype. Finally, multiple hotspot mutations in protein-protein interaction domains critical for cell polarity were identified. Our data indicate that genomic events likely contribute to pervasive disruption of epithelial polarity observed in invasive breast cancer.

Magnetic vortex states in chromium(IV) oxide (CrO2)

As an exploration for probable magnetic vortex state in chromium(IV) oxide (CrO2), we performed micro-magnetic simulations on CrO2 nanodiscs. For our simulation studies, we considered CrO2 nanodiscs with 100 nm diameter and 20 nm thickness. After the ferromagnetic positive or negative saturation, when the applied magnetic field along the ±x-axis was reduced, vortex states with its magnetization winding in xy-plane nucleated in the CrO2 nanodisc at ∓12 mT, and annihilated at ∓41 mT. The magnetic vortex states were found to be stable even after reducing the applied magnetic field to 0 mT. Further, switching the magnetic vortex core polarity pointing up to down and vice versa using DC as well as AC magnetic fields has been simulated. The magnetization of the vortex core instantaneously flipped by an applied DC magnetic field of ±138 mT and within 2 ns by applied 6 GHz resonance AC magnetic field with 8 mT amplitude. Furthermore, we present a comparison about the formation, remanent state and switching of the magnetic vortex state in CrO2 nanodisc with that of the most widely studied permalloy nanodisc having same dimensions.

Primary Cilia Reconsidered in the Context of Ciliopathies: Extraciliary and Ciliary Functions of Cilia Proteins Converge on a Polarity theme?

Once dismissed as vestigial organelles, primary cilia have garnered the interest of scientists, given their importance in development/signaling, and for their implication in a new disease category known as ciliopathies. However, many, if not all, "cilia" proteins also have locations/functions outside of the primary cilium. These extraciliary functions can complicate the interpretation of a particular ciliopathy phenotype: it may be a result of defects at the cilium and/or at extraciliary locations, and it could be broadly related to a unifying cellular process for these proteins, such as polarity. Assembly of a cilium has many similarities to the development of other polarized structures. This evolutionarily preserved process for the assembly of polarized cell structures offers a perspective on how the cilium may have evolved. We hypothesize that cilia proteins are critical for cell polarity, and that core polarity proteins may have been specialized to form various cellular protrusions, including primary cilia.

Subnanosecond Radial Vortex Core Polarity Reversal Using Linearly Attenuated Perpendicular Magnetic Field

The dynamic properties of radial vortex core (RVC) polarity reversal in PtCo20Fe60B 20Ti multilayers induced by a linearly attenuated perpendicular magnetic field are investigated. Micromagnetic simulation indicates that the polarity of the RVC can be quickly reversed through a continuous distortion of circular chirality around the core. The reversal time can be reduced to below one nanosecond when the magnitudes of the magnetic field and the attenuation time are selected properly. A quantitative analysis of the core exchange-energy density, Zeeman energy density, and magnetostatic energy density explains the RVC polarity reversal. At the moment of RVC polarity switching, the exchange energy density is sharply reduced, accompanied by the emission of strong spin waves. This scheme provides a new method to achieve ultra-fast RVC polarity reversal, which lays a foundation for radial vortex-based magnetoresistive memory devices.

Disruption of Core Planar Cell Polarity Signaling Regulates Renal Tubule Morphogenesis but Is Not Cystogenic

Oriented cell division (OCD) and convergent extension (CE) shape developing renal tubules, and their disruption has been associated with polycystic kidney disease (PKD) genes, the majority of which encode proteins that localize to primary cilia. Core planar cell polarity (PCP) signaling controls OCD and CE in other contexts, leading to the hypothesis that disruption of PCP signaling interferes with CE and/or OCD to produce PKD. Nonetheless, the contribution of PCP to tubulogenesis and cystogenesis is uncertain, and two major questions remain unanswered. Specifically, the inference that mutation of PKD genes interferes with PCP signaling is untested, and the importance of PCP signaling for cystogenic PKD phenotypes has not been examined. We show that, during proliferative stages, PCP signaling polarizes renal tubules to control OCD. However, we find that, contrary to the prevailing model, PKD mutations do not disrupt PCP signaling but instead act independently and in parallel with PCP signaling to affect OCD. Indeed, PCP signaling that is normally downregulated once development is completed is retained in cystic adult kidneys. Disrupting PCP signaling results in inaccurate control of tubule diameter, a tightly regulated parameter with important physiological ramifications. However, we show that disruption of PCP signaling is not cystogenic. Our results suggest that regulating tubule diameter is a key function of PCP signaling but that loss of this control does not induce cysts.

Cell Polarity in Yeast.

A conserved molecular machinery centered on the Cdc42 GTPase regulates cell polarity in diverse organisms. Here we review findings from budding and fission yeasts that reveal both a conserved core polarity circuit and several adaptations that each organism exploits to fulfill the needs of its lifestyle. The core circuit involves positive feedback by local activation of Cdc42 to generate a cluster of concentrated GTP-Cdc42 at the membrane. Species-specific pathways regulate the timing of polarization during the cell cycle, as well as the location and number of polarity sites.

Secondary‐Structure‐Driven Self‐Assembly of Reactive Polypept(o)ides: Controlling Size, Shape, and Function of Core Cross‐Linked Nanostructures

Achieving precise control over the morphology and function of polymeric nanostructures during self-assembly remains a challenge in materials as well as biomedical science, especially when independent control over particle properties is desired. Herein, we report on nanostructures derived from amphiphilic block copolypept(o)ides by secondary-structure-directed self-assembly, presenting a strategy to adjust core polarity and function separately from particle preparation in a bioreversible manner. The peptide-inherent process of secondary-structure formation allows for the synthesis of spherical and worm-like core-cross-linked architectures from the same block copolymer, introducing a simple yet powerful approach to versatile peptide-based core-shell nanostructures.

Meru couples planar cell polarity with apical-basal polarity during asymmetric cell division.

Polarity is a shared feature of most cells. In epithelia, apical-basal polarity often coexists, and sometimes intersects with planar cell polarity (PCP), which orients cells in the epithelial plane. From a limited set of core building blocks (e.g. the Par complexes for apical-basal polarity and the Frizzled/Dishevelled complex for PCP), a diverse array of polarized cells and tissues are generated. This suggests the existence of little-studied tissue-specific factors that rewire the core polarity modules to the appropriate conformation. In Drosophila sensory organ precursors (SOPs), the core PCP components initiate the planar polarization of apical-basal determinants, ensuring asymmetric division into daughter cells of different fates. We show that Meru, a RASSF9/RASSF10 homologue, is expressed specifically in SOPs, recruited to the posterior cortex by Frizzled/Dishevelled, and in turn polarizes the apical-basal polarity factor Bazooka (Par3). Thus, Meru belongs to a class of proteins that act cell/tissue-specifically to remodel the core polarity machinery.

Substitution Effects on the Photoinduced Charge-Transfer Properties of Novel Perylene-3,4,9,10-tetracarboxylic Acid Derivatives.

We report here the synthesis and photophysical study of a series of electron donor–acceptor molecules, in which electron-donating 4-methoxyphenoxy groups are attached to the 1,7-bay positions of four different perylene tetracarboxylic acid derivatives, namely, perylene tetraesters 1, perylene monoimide diesters 2, perylene bisimides 3, and perylene monobenzimidazole monoimides 4. These perylene derivatives are used because of their increasing order of electron-accepting capability upon moving from 1 to 4. Two additional donor–acceptor molecules are synthesized by linking electron-donating 4-methoxyphenyl groups to the imide position of perylene monoimide diester 2 and perylene bisimide 3. The motivation for this study is to achieve a good control over the photoinduced charge-transfer (CT) process in perylene-based systems by altering the position of electron donors and tuning the electron deficiency of perylene core. A comprehensive study of the photophysical properties of these molecules has shown a highly systematic trend in the magnitude of CT as a function of increased electron deficiency of the perylene core and solvent polarity. Importantly, just by changing the attachment of electron-donating group from “bay” to “imide” position, we are able to block the CT process. This implies that the positioning of the electron donor at the perylene core strongly influences the kinetics of the photoinduced CT process. In these compounds, the CT process is characterized by the quenching of fluorescence and singlet excited-state lifetimes as compared to model compounds bearing non-electron-donating 4-tert-butylphenoxy groups. Transient absorption spectroscopy did not reveal spectra of CT states. This most likely implies that the CT state is not accumulated, because of the faster charge recombination.

Reconfigurable magnetic domain wall pinning using vortex-generated magnetic fields

Although often important for domain wall device applications, reproducible fabrication of pinning sites at the nano-scale remains challenging. Here, we demonstrate that the stray magnetic field generated beneath magnetic vortex cores can be used to generate localized pinning sites for magnetic domain walls in an underlying, perpendicularly magnetized nanostrip. Moreover, we show that the pinning strength can be tuned by switching the vortex core polarity: switching the core polarity so that it is aligned with the magnetization of the expanding domain (rather than against it) can reduce the vortex-mediated wall depinning field by between 40% and 90%, depending on the system geometry. Significant reductions in the depinning field are also demonstrated in narrow strips by shifting the core away from the strips' centers.

A Phenotypic High-Content Screening Assay to Identify Regulators of Membrane Protein Localization.

Correct subcellular localization of proteins is a requirement for appropriate function. This is especially true in epithelial cells, which rely on the precise localization of a diverse array of epithelial polarity and cellular adhesion proteins. Loss of cell polarity and adhesion is a hallmark of cancer, and mislocalization of core polarity proteins, such as Scribble, is observed in a range of human epithelial tumors and is prognostic of poor survival. Despite this, little is known about how Scribble membrane localization is regulated. Here, we describe the development and application of a phenotypic high-content screening assay that is designed to specifically quantify membrane levels of Scribble to identify regulators of its membrane localization. A screening platform that is capable of resolving individual cells and quantifying membrane protein localization in confluent epithelial monolayers was developed by using the cytoplasm-to-cell-membrane bioapplication integrated with the Cellomics ArrayScan high-content imaging platform. Application of this method to a boutique human epithelial polarity and signaling small interfering RNA (siRNA) library resulted in highly robust coefficient-of-variance and Z' factor values. As proof of concept, we present two candidate genes whose depletion specifically reduces Scribble protein levels at the membrane. Data mining revealed that these proteins interact with components of the Scribble polarity complex, providing support for the utility of the screening approach. This method is broadly applicable to genome-wide and large-scale compound screening of membrane-bound proteins, and when coupled with pathway analysis the dataset becomes even more valuable and can provide predictive mechanistic insight.

Magnetic vortex racetrack memory

We report a new type of racetrack memory based on current-controlled movement of magnetic vortices in magnetic nanowires with rectangular cross-section and weak perpendicular anisotropy. Data are stored through the core polarity of vortices and each vortex carries a data bit. Besides high density, non-volatility, fast data access, and low power as offered by domain wall racetrack memory, magnetic vortex racetrack memory has additional advantages of no need for constrictions to define data bits, changeable information density, adjustable current magnitude for data propagation, and versatile means of ultrafast vortex core switching. By using micromagnetic simulations, current-controlled motion of magnetic vortices in cobalt nanowire is demonstrated for racetrack memory applications.

Electrical measurement of magnetic-field-impeded polarity switching of a ferromagnetic vortex core

Vortex core polarity switching in NiFe disks has been evidenced using an all-electrical rectification scheme. Both simulation and experiments yield a consistent loss of the rectified signal when driving the core at high powers near its gyrotropic resonant frequency. The frequency range over which the loss occurs grows and shifts with increasing signal power, consistent with non-linear core dynamics and periodic switching of the core polarity induced by the core attaining its critical velocity. We demonstrate that core polarity switching can be impeded by displacing the core towards the disk's edge where an increased core stiffness reduces the maximum attainable core velocity.

Magnetic Radial Vortex Stabilization and Efficient Manipulation Driven by the Dzyaloshinskii-Moriya Interaction and Spin-Transfer Torque.

Solitons are very promising for the design of the next generation of ultralow power devices for storage and computation. The key ingredient to achieving this goal is the fundamental understanding of their stabilization and manipulation. Here, we show how the interfacial Dzyaloshinskii-Moriya Interaction (IDMI) is able to lift the energy degeneracy of a magnetic vortex state by stabilizing a topological soliton with radial chirality, hereafter called radial vortex. It has a noninteger Skyrmion number S (0.5<|S|<1) due to both the vortex core polarity and the magnetization tilting induced by the IDMI boundary conditions. Micromagnetic simulations predict that a magnetoresistive memory based on the radial vortex state in both free and polarizer layers can be efficiently switched by a threshold current density smaller than 10^{6} A/cm^{2}. The switching processes occur via the nucleation of topologically connected vortices and vortex-antivortex pairs, followed by spin-wave emissions due to vortex-antivortex annihilations.

Numerical analysis of inductive detection of magnetic vortex motion excited with circularly polarized field

In the present study, the rotation and switching of a vortex core in submicron-size square dots were numerically analyzed by micromagnetic simulation. This study clarified that the eigenfrequency of the vortex core is strongly dependent on the magnetostatic energy and that rapid switching can be realized by circularly polarized fields with practical amplitudes at the corresponding eigenfrequency. The inductive detection of vortex core rotation, which can distinguish vortex core polarity, was successfully demonstrated and the structural design of the detector was optimized.

Unconventional spin distributions in thick Ni80Fe20 nanodisks

We study the spin distributions in permalloy (Py: Ni80Fe20) nanodisks as a function of diameter D (300 nm ≤ D ≤ 1 μm) and thickness L (30 nm ≤ L ≤ 100 nm). We observed that beyond a certain thickness, for a fixed disk diameter, an unconventional spin topology precipitates which is marked by the presence of a divergence field within the magnetic vortex curl. The strength of this divergence changes anti-symmetrically from negative to positive—depending on the core polarity—along the axis of the cylindrical nanodisk. This is also accompanied by a skyrmion-like out-of-plane bending of the spin vectors farther away from the disk center. Additionally, the vortex core dilates significantly when compared to its typical size. This has been directly observed using magnetic force microscopy. We determined from the ferromagnetic resonance spectroscopy measurements that the unconventional topology in the thicker nanodisks gyrated at a frequency, which is significantly lower than what is predicted by a magnetic vortex based analytical model. Micromagnetic simulations involving dipolar and exchange interactions appear to satisfactorily reproduce the experimentally observed static and dynamic behaviors. Besides providing a physical example of an unconventional topology, these results can also aid the design of topologically protected memory elements.