127 research outputs found

    Insulated conducting cantilevered nanotips and two-chamber recording system for high resolution ion sensing AFM.

    Get PDF
    Biological membranes contain ion channels, which are nanoscale pores allowing controlled ionic transport and mediating key biological functions underlying normal/abnormal living. Synthetic membranes with defined pores are being developed to control various processes, including filtration of pollutants, charge transport for energy storage, and separation of fluids and molecules. Although ionic transport (currents) can be measured with single channel resolution, imaging their structure and ionic currents simultaneously is difficult. Atomic force microscopy enables high resolution imaging of nanoscale structures and can be modified to measure ionic currents simultaneously. Moreover, the ionic currents can also be used to image structures. A simple method for fabricating conducting AFM cantilevers to image pore structures at high resolution is reported. Tungsten microwires with nanoscale tips are insulated except at the apex. This allows simultaneous imaging via cantilever deflections in normal AFM force feedback mode as well as measuring localized ionic currents. These novel probes measure ionic currents as small as picoampere while providing nanoscale spatial resolution surface topography and is suitable for measuring ionic currents and conductance of biological ion channels

    Structure and permeability of ion-channels by integrated AFM and waveguide TIRF microscopy.

    Get PDF
    Membrane ion channels regulate key cellular functions and their activity is dependent on their 3D structure. Atomic force microscopy (AFM) images 3D structure of membrane channels placed on a solid substrate. Solid substrate prevents molecular transport through ion channels thus hindering any direct structure-function relationship analysis. Here we designed a ~70 nm nanopore to suspend a membrane, allowing fluidic access to both sides. We used these nanopores with AFM and total internal reflection fluorescence microscopy (TIRFM) for high resolution imaging and molecular transport measurement. Significantly, membranes over the nanopore were stable for repeated AFM imaging. We studied structure-activity relationship of gap junction hemichannels reconstituted in lipid bilayers. Individual hemichannels in the membrane overlying the nanopore were resolved and transport of hemichannel-permeant LY dye was visualized when the hemichannel was opened by lowering calcium in the medium. This integrated technique will allow direct structure-permeability relationship of many ion channels and receptors

    Role of the fast kinetics of pyroglutamate-modified amyloid-β oligomers in membrane binding and membrane permeability.

    Get PDF
    Membrane permeability to ions and small molecules is believed to be a critical step in the pathology of Alzheimer's disease (AD). Interactions of oligomers formed by amyloid-β (Aβ) peptides with the plasma cell membrane are believed to play a fundamental role in the processes leading to membrane permeability. Among the family of Aβs, pyroglutamate (pE)-modified Aβ peptides constitute the most abundant oligomeric species in the brains of AD patients. Although membrane permeability mechanisms have been studied for full-length Aβ1-40/42 peptides, these have not been sufficiently characterized for the more abundant AβpE3-42 fragment. Here we have compared the adsorbed and membrane-inserted oligomeric species of AβpE3-42 and Aβ1-42 peptides. We find lower concentrations and larger dimensions for both species of membrane-associated AβpE3-42 oligomers. The larger dimensions are attributed to the faster self-assembly kinetics of AβpE3-42, and the lower concentrations are attributed to weaker interactions with zwitterionic lipid headgroups. While adsorbed oligomers produced little or no significant membrane structural damage, increased membrane permeabilization to ionic species is understood in terms of enlarged membrane-inserted oligomers. Membrane-inserted AβpE3-42 oligomers were also found to modify the mechanical properties of the membrane. Taken together, our results suggest that membrane-inserted oligomers are the primary species responsible for membrane permeability

    Mobile application for the timely detection of potential COVID-19 infections

    Get PDF
    The objective of this study is to determine user acceptance of a mobile application for the timely detection of possible COVID-19 infections in the city of Cajamarca. For this purpose, the mobile application Covid Alerta (Covid Alert) was developed for devices with the Android operating system. The OpenUp software development methodology was used for the development of this application. The applied, quantitative, exploratory research used 2 survey forms: one to measure how the detection of COVID-19 was carried out in the city of Cajamarca, and another to measure the impact of using a mobile application to detect infected contacts. The results indicated that the most reliable screening tests are molecular tests; in addition, 85% of respondents felt much safer receiving alerts of infected contacts on their mobile devices. Likewise, 88.5% indicated confidently that the application complies with registering and reporting infected contacts. This shows that 88.8% of users accepted the use of mobile applications for the timely detection of possible COVID-19 infections

    Structural Convergence Among Diverse, Toxic β-Sheet Ion Channels

    Get PDF
    Recent studies show that an array of -sheet peptides, including N-terminally truncated A peptides (A11-42/17-42), K3 (a 2-microglobulin fragment), and protegrin-1 (PG-1) peptides form ion channel-like structures and elicit single channel ion conductance when reconstituted in lipid bilayers and induce cell damage through cell calcium overload. Striking similarities are observed in the dimensions of these toxic channels irrespective of their amino acid sequences. However, the intriguing question of preferred channel sizes is still unresolved. Here, exploiting ssNMR-based, U-shaped, -strand-turn--strand coordinates, we modeled truncated A peptide (p3) channels with different sizes (12- to 36-mer). Molecular dynamics (MD) simulations show that optimal channel sizes of the ion channels presenting toxic ionic flux range between 16- and 24-mer. This observation is in good agreement with channel dimensions imaged by AFM for A9-42, K3 fragment, and PG-1 channels and highlights the bilayer-supported preferred toxic -channel sizes and organization, regardless of the peptide sequence

    Note: Vectorial-magneto optical Kerr effect technique combined with variable temperature and full angular range all in a single setup

    Full text link
    Here, we report on a versatile full angular resolved/broad temperature range/vectorial magneto optical Kerr effect (MOKE) magnetometer, named TRISTAN. Its versatility relies on its capacity to probe temperature and angular dependencies of magnetization reversal processes without the need to do any intervention on the apparatus during measurements. The setup is a combination of a vectorial MOKE bench and a cryostat with optical access. The cryostat has a motorized rotatable sample holder with azimuthal correction. It allows for simultaneous and quantitative acquisition of the two in-plane magnetization components during the hysteresis loop at different temperatures from 4 K up to 500 K and in the whole angular range, without neither changing magnet orientation nor opening the cryostat. Measurements performed in a model system with competing collinear biaxial and uniaxial contributions are presented to illustrate its capabilitiesP.P. acknowledges financial support from MINECO through Contract No. JCI-2011- 09602. F.J.T. acknowledges financial support from Ramon y Cajal program (RYC-2011-09617). This work has been supported by MINECO through Project Nos. MAT2011-25598 and MAT2012-39308, by the Comunidad de Madrid through Project No. S2013/MIT-2850 NANOFRONTMAG-CM and by EU-FP7 through NANOPYME Project (No. 310516

    Tarjeta de adquisición y tratamiento de señales mioeléctrica de tres canales para prótesis trans-radiales

    Get PDF
    With the advancement of technology, it has been increasingly successful to improve the construction of prostheses asextensions of a member of the human body. For the functionality of many of them, it is necessary to use acquisition cards and signalprocessing. In the case of trans-radial amputations, the connection area or socket is small, which leads to the problem of how toimplement a card that is capable of acquiring three signals and decreasing the number of electrodes to be connected. To meet theserequirements we proceeded to design a first prototype with the main goal of being a light, small and three-channel measuring system. Acommon ground configuration was used in order to decrease the number of electrodes. In this way, it has great impact and functionalityin the area since it will be possible to continue the rest of the research in the field of control systems applied to myoelectric prostheses.This article describes the process of designing, implementing, testing and analyzing results.Con el avance de la tecnología se ha logrado cada vez más mejorar la construcción de prótesis como extensiones dealgún miembro del cuerpo humano. Para la funcionalidad de muchas de ellas se hace necesario el uso de tarjetas de adquisición yprocesamiento de las señales. En el caso de las amputaciones trans-radiales el área de conexión o socket es de tamaño reducido, lo cualconduce al problema de cómo implementar una tarjeta que sea capaz de adquirir tres señales y que disminuya el número de electrodosa conectar. Para cumplir con estos requisitos se procedió a diseñar e implementar un primer prototipo con la principal meta de que seaun sistema ligero, pequeño y de tres canales de medición. Se utilizó una configuración de tierra común con la finalidad de disminuir lacantidad de electrodos. De esta manera, se tiene gran impacto y funcionalidad en el área, ya que se podrá continuar con el resto de lasinvestigaciones en el campo de los sistemas de control aplicados a prótesis mioeléctricas. Este artículo describe el proceso de diseño,implementación, prueba y análisis de los resultados
    corecore