{"id":95730,"date":"2022-06-10T08:32:24","date_gmt":"2022-06-10T06:32:24","guid":{"rendered":"https:\/\/testweb.ibecbarcelona.eu\/mechanosensing-harnessing-nuclear-mechanics-to-understand-health-and-disease\/"},"modified":"2022-07-16T12:46:21","modified_gmt":"2022-07-16T10:46:21","slug":"mechanosensing-harnessing-nuclear-mechanics-to-understand-health-and-disease","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/es\/mechanosensing-harnessing-nuclear-mechanics-to-understand-health-and-disease\/","title":{"rendered":"Mecanotransducci\u00f3n: aplicaci\u00f3n de la mec\u00e1nica nuclear para comprender la salud y la enfermedad"},"content":{"rendered":"\n

Un estudio liderado por investigadores del IBEC y publicado hoy en la revista Nature Cell Biology demuestra que la aplicaci\u00f3n de fuerza mec\u00e1nica al n\u00facleo celular afecta al transporte de prote\u00ednas a trav\u00e9s de la membrana nuclear. Esta acci\u00f3n controla los procesos celulares y podr\u00eda desempe\u00f1ar un papel clave en diversas enfermedades, como el c\u00e1ncer. Esto implica un enfoque novedoso para comprender los aspectos de la invasi\u00f3n del c\u00e1ncer y la met\u00e1stasis, abriendo puertas a nuevas t\u00e9cnicas potenciales tanto diagn\u00f3sticas como terap\u00e9uticas.<\/h4>\n\n\n\n
\"\"<\/figure><\/div>\n\n\n\n

Las c\u00e9lulas de nuestro cuerpo perciben los est\u00edmulos mec\u00e1nicos de su entorno y responden en consecuencia, tomando decisiones sobre c\u00f3mo y cu\u00e1ndo crecer, moverse y diferenciarse, este proceso se conoce como mecanotransducci\u00f3n y es de vital importancia para la funci\u00f3n celular y, en \u00faltima instancia, para la salud humana.<\/p>\n\n\n\n

En un estudio liderado por el investigador del IBEC Pere Roca-Cusachs y publicado hoy en la revista Nature Cell Biology, se ha demostrado que la aplicaci\u00f3n directa de fuerza al n\u00facleo puede afectar la organizaci\u00f3n espacial del ADN y la actividad de las prote\u00ednas nucleares, entre otros. Cuando las c\u00e9lulas tumorales invaden los \u00f3rganos y se produce la met\u00e1stasi, por ejemplo, se generan fuerzas f\u00edsicas que se transmiten hasta el n\u00facleo celular. Estas fuerzas afectan dr\u00e1sticamente la expresi\u00f3n g\u00e9nica e impulsan la progresi\u00f3n de la enfermedad.<\/p>\n\n\n\n

\u201cLa mecanotransducci\u00f3n nuclear juega un papel central en la progresi\u00f3n del c\u00e1ncer al regular el crecimiento tumoral, la invasi\u00f3n y la met\u00e1stasis. Sin embargo, los mecanismos subyacentes a la mecanotransducci\u00f3n nuclear a\u00fan se desconocen en gran medida. La raz\u00f3n principal de esto es la falta de una tecnolog\u00eda que nos permita visualizar lo que ocurre dentro del n\u00facleo cuando est\u00e1 sujeto a una fuerza mec\u00e1nica\u201d, comenta Pere Roca-Cusachs, investigador principal del IBEC y profesor agregado de la Universidad de Barcelona.<\/p>\n\n\n\n

En este trabajo, los investigadores \u200b\u200bhan identificado un mecanismo subyacente a la mecanotransducci\u00f3n nuclear, mostrando c\u00f3mo la aplicaci\u00f3n de fuerzas f\u00edsicas al n\u00facleo afectaba al transporte de prote\u00ednas a trav\u00e9s de la membrana nuclear y su consiguiente distribuci\u00f3n entre el citoplasma y el n\u00facleo.<\/p>\n\n\n\n

\u201cEs bien sabido que las fuerzas mec\u00e1nicas afectan la expresi\u00f3n g\u00e9nica. Nuestro trabajo revela un mecanismo que explica c\u00f3mo ocurre esto\u201d, explican Ion Andreu (primer coautor) e Ignasi Granero (primer coautor).<\/p>\n\n\n\n

Este trabajo se ha realizado en colaboraci\u00f3n con el grupo de modelado te\u00f3rico de Barak Raveh (Universidad Hebrea de Jerusal\u00e9n) y el Francis Crick Institute.<\/p>\n\n\n\n

Forzar el movimiento de prote\u00ednas<\/strong><\/p>\n\n\n\n

Las prote\u00ednas viajan del n\u00facleo al citoplasma, y \u200b\u200bviceversa, a trav\u00e9s de estructuras espec\u00edficas denominadas Complejos de Poros Nucleares (NPCs) principalmente de dos maneras: difusi\u00f3n activa y pasiva. El transporte pasivo es r\u00e1pido para prote\u00ednas peque\u00f1as, pero se reduce progresivamente a medida que aumenta el peso molecular de la prote\u00edna. El transporte activo de mol\u00e9culas m\u00e1s grandes depende de los receptores de transporte nuclear que interact\u00faan con ellos uni\u00e9ndose a secuencias espec\u00edficas, conocidas como Se\u00f1ales de Localizaci\u00f3n Nuclear (NLS, para prote\u00ednas que entran en el n\u00facleo) o Se\u00f1ales de Exportaci\u00f3n Nuclear (NES, para prote\u00ednas que salen del n\u00facleo).<\/p>\n\n\n\n

Los autores encontraron que la aplicaci\u00f3n de fuerzas f\u00edsicas al n\u00facleo mejoraba la permeabilidad a trav\u00e9s de los NPCs, lo que aumentaba el transporte de mol\u00e9culas. Adem\u00e1s, encontraron que el transporte activo aumentaba m\u00e1s que la difusi\u00f3n pasiva. Esta respuesta diferencial conduce a cambios en el transporte de mol\u00e9culas a trav\u00e9s de NPCs en funci\u00f3n de la fuerza.<\/p>\n\n\n\n

Los autores dise\u00f1aron mol\u00e9culas mecanosensibles ajustando su difusi\u00f3n pasiva a trav\u00e9s de NPCs (cambiando su peso molecular) y su transporte activo (introduciendo secuencias espec\u00edficas de NLS o NES). Al incluir un marcador fluorescente en estas mol\u00e9culas, generaron indicadores fluorescentes que entran o salen del n\u00facleo por la fuerza.<\/p>\n\n\n\n

El potencial terap\u00e9utico de la mecanotransducci\u00f3n<\/strong><\/p>\n\n\n\n

Mediante la optimizaci\u00f3n y combinaci\u00f3n adecuada de estos constructos, los grupos liderados por Pere Roca-Cusachs y Xavier Trepat del IBEC pretenden desarrollar sensores emisores de luz que midan la mecanotransducci\u00f3n nuclear mediante el seguimiento de su localizaci\u00f3n nuclear. Este trabajo se enmarca en un ambicioso proyecto financiado por la Convocatoria CaixaResearch de Investigaci\u00f3n en Salud de la Fundaci\u00f3n \u201cla Caixa\u201d.<\/p>\n\n\n\n

Para calibrar y validar los sensores, los investigadores utilizar\u00e1n posteriormente modelos animales de c\u00e1ncer de mama y colorrectal. Introducir\u00e1n los sensores en c\u00e9lulas cancerosas tanto de estos tejidos como de ratones, y seguir\u00e1n su comportamiento utilizando t\u00e9cnicas de microscop\u00eda avanzadas. De esta manera, podr\u00e1n mapear la mecanotransducci\u00f3n durante la invasi\u00f3n y met\u00e1stasis del c\u00e1ncer.<\/p>\n\n\n\n

Este trabajo establece un marco novedoso para comprender c\u00f3mo la mec\u00e1nica impulsa la progresi\u00f3n del c\u00e1ncer, abriendo la puerta a nuevas t\u00e9cnicas potenciales tanto diagn\u00f3sticas como terap\u00e9uticas.<\/p>\n\n\n\n

Reference article: <\/strong>Ion Andreu, Ignasi Granero-Moya, Nimesh R. Chahare, Kessem Clein, Marc Molina-Jord\u00e1n, Amy E. M. Beedle, Alberto Elosegui-Artola, Juan F. Abenza, Leone Rossetti, Xavier Trepat, Barak Raveh & Pere Roca-Cusachs.  Mechanical force application to the nucleus regulates nucleocytoplasmic transport. Nat Cell Biol<\/em> (2022). https:\/\/doi.org\/10.1038\/s41556-022-00927-7<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

A study led by IBEC researchers, and published in Nature Cell Biology, shows that applying mechanical force to the cell nucleus affects the transport of proteins across the nuclear membrane. In doing so, this controls cellular processes and could play a key role in various diseases, such as cancer. This entails a novel approach to understanding aspects of cancer invasion and metastasis, opening the door to potential new techniques for diagnosis and therapy.<\/H3><\/p>\n","protected":false},"author":4,"featured_media":95472,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[97],"tags":[1725,1135],"post_formats":[],"class_list":["post-95730","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticias-de-investigacion","tag-mechanosensing-es","tag-pere-roca-cusachs-es"],"yoast_head":"\nMecanotransducci\u00f3n: aplicaci\u00f3n de la mec\u00e1nica nuclear para comprender la salud y la enfermedad - Institute for Bioengineering of Catalonia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ibecbarcelona.eu\/es\/mechanosensing-harnessing-nuclear-mechanics-to-understand-health-and-disease\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Mecanotransducci\u00f3n: aplicaci\u00f3n de la mec\u00e1nica nuclear para comprender la salud y la enfermedad - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"A study led by IBEC researchers, and published in Nature Cell Biology, shows that applying mechanical force to the cell nucleus affects the transport of proteins across the nuclear membrane. 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