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Mechanically-gated Ion Channels01:12

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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
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Voltage-gated Ion Channels01:26

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Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
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Non-gated Ion Channels01:24

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Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
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Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
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Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
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Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

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Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
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Canales de iones sintéticos sensibles a la mecánica

Takahiro Muraoka1,2, Kaori Umetsu3, Kazuhito V Tabata4

  • 1School of Life Science and Technology, Tokyo Institute of Technology , 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan.

Journal of the American Chemical Society
|October 28, 2017
PubMed
Resumen

Los investigadores desarrollaron moléculas sintéticas que imitan las proteínas de la membrana celular que detectan el estrés mecánico. Estas anfifilas sensibles a la tensión muestran potencial para crear nuevos dispositivos moleculares mecano-sensibles.

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Área de la Ciencia:

  • Ciencia de los biomateriales
  • Ingeniería molecular
  • Química supramolecular

Sus antecedentes:

  • El estrés mecánico es un estímulo clave para los sistemas biológicos, detectado principalmente por las proteínas de la membrana.
  • Las moléculas sintéticas rara vez muestran sensibilidad a las fuerzas mecánicas, lo que limita el desarrollo de dispositivos mecano-responsivos.
  • Los canales iónicos mecano-sensibles en las membranas celulares proporcionan un modelo biológico para la detección de la fuerza.

Objetivo del estudio:

  • Para diseñar y sintetizar nuevos anfífilos transmembrana sensibles a la tensión.
  • Investigar la respuesta mecánica y las capacidades de transporte de iones de estas moléculas sintéticas.
  • Para comparar las fuerzas operativas de los sistemas sintéticos con las proteínas mecano-sensibles naturales.

Principales métodos:

  • Desarrollo de anfífilos de una y tres transmembranas.
  • Incorporación de anfífilos en las membranas lipídicas.
  • Análisis espectroscópico para evaluar el apilamiento molecular y la respuesta a la tensión.
  • Pruebas de transporte de iones en condiciones de tensión mecánica variables.

Principales resultados:

  • Los anfífilos de transmembrana única mostraron debilitamiento y fortalecimiento dependientes de la tensión de la acumulación molecular, lo que desencadenó el transporte de iones bajo tensión en expansión.
  • Los anfífilos de tres transmembranas formaron canales unimoleculares para el transporte de iones incluso sin tensión, con una actividad decreciente bajo tensión en expansión.
  • Se encontró que las fuerzas operativas de estos sistemas sintéticos eran comparables a las de las proteínas mecano-sensibles naturales.

Conclusiones:

  • Las anfifilas transmembrana sintéticas pueden ser diseñadas para responder a la tensión mecánica.
  • Las diferentes arquitecturas moleculares (una sola frente a tres transmembranas) exhiben distintos mecanismos de respuesta a la tensión y comportamientos de transporte de iones.
  • Esta investigación allana el camino para el desarrollo de nuevos dispositivos moleculares sintéticos mecano-sensibles.