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Los receptores de membrana químicamente sintéticos establecen células con vías de señalización de sentido y respuesta
Hui Wu1, Linyan Zheng1, Neng Ling1
1Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
Journal of the American Chemical Society
|January 19, 2023
Resumen
Los investigadores crearon un receptor sintético usando ADN y péptidos para dar a las células nuevas capacidades de detección de pH. Este receptor artificial puede activar las vías de señalización celular en respuesta a los cambios de pH externos.
Área de la Ciencia:
- Biología sintética
- Ingeniería celular
- Biotecnología
Sus antecedentes:
- Las células requieren mecanismos sofisticados para detectar y responder a las señales ambientales.
- El desarrollo de sistemas artificiales para la comunicación celular y las respuestas de ingeniería es un desafío significativo.
- Los receptores sintéticos ofrecen una vía prometedora para expandir las capacidades celulares.
Objetivo del estudio:
- Diseñar un nuevo receptor sintético anclado en la membrana (Ts-pHLIP-Pr) capaz de detectar estímulos de pH externos.
- Establecer vías de señalización artificiales dentro de las células utilizando bloques de construcción de ADN y péptidos.
- Para demostrar la capacidad del receptor para desencadenar eventos celulares aguas abajo en respuesta a los cambios de pH.
Principales métodos:
- Construcción de un receptor sintético anclado en la membrana (Ts-pHLIP-Pr) utilizando componentes de ADN y péptidos.
- Aprovechando el interruptor conformacional sensible al pH del péptido pHLIP para la translocación de la membrana.
- Utilizando el receptor translocado para reclutar proteínas específicas e iniciar cascadas de señalización.
- Validación experimental de la función de Ts-pHLIP-Pr en la regulación de la señalización de la proteína quinasa C epsilon (PKCε).
Principales resultados:
- El Ts-pHLIP-Pr confiere con éxito capacidades de detección y respuesta de pH a las células.
- Se ha demostrado la regulación de los eventos de señalización relacionados con la PKCε provocados por la reducción del pH externo.
- Mostró la modularidad del receptor para la activación potencial de las células T a través de la translocación ZAP70 en entornos de bajo pH.
Conclusiones:
- El receptor Ts-pHLIP-Pr desarrollado permite a las células detectar y responder a los cambios de pH externos.
- Este receptor sintético proporciona un nuevo método para diseñar vías de señalización artificial en las células.
- Los hallazgos presentan un nuevo paradigma para la biología sintética inteligente y las aplicaciones de ingeniería celular personalizadas.
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