{"id":94930,"date":"2022-06-10T08:32:24","date_gmt":"2022-06-10T06:32:24","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/mechanosensing-harnessing-nuclear-mechanics-to-understand-health-and-disease\/"},"modified":"2022-07-15T15:08:03","modified_gmt":"2022-07-15T13:08:03","slug":"mechanosensing-harnessing-nuclear-mechanics-to-understand-health-and-disease","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/mechanosensing-harnessing-nuclear-mechanics-to-understand-health-and-disease\/","title":{"rendered":"Mecanotransducci\u00f3: aplicaci\u00f3 de la mec\u00e0nica nuclear per a comprendre la salut i la malaltia"},"content":{"rendered":"

Les c\u00e8l\u00b7lules del nostre cos perceben els est\u00edmuls mec\u00e0nics del seu entorn i responen en conseq\u00fc\u00e8ncia, prenent decisions sobre com i quan cr\u00e9ixer, moure’s i diferenciar-se. El proc\u00e9s es coneix com mecanotransducci\u00f3 i \u00e9s de vital import\u00e0ncia per a la funci\u00f3 cel\u00b7lular i, en \u00faltima inst\u00e0ncia, per a la salut humana.<\/p>\n

\"\"En un estudi liderat per l\u2019investigadro de l\u2019IBEC Pere Roca-Cusachs i publicat avui a la revista Nature Cell Biology, s’ha demostrat que l’aplicaci\u00f3 directa de for\u00e7a al nucli pot afectar l’organitzaci\u00f3 espacial de l’ADN i l’activitat de les prote\u00efnes nuclears, entre altres. Quan les c\u00e8l\u00b7lules tumorals envaeixen els \u00f2rgans i es produeix met\u00e0stasis, per exemple, generen forces f\u00edsiques que es transmeten fins al nucli cel\u00b7lular. Aquestes forces afecten dr\u00e0sticament l’expressi\u00f3 g\u00e8nica i impulsen la progressi\u00f3 de la malaltia.<\/p>\n

\u201cLa mecanotransducci\u00f3 nuclear juga un paper central en la progressi\u00f3 del c\u00e0ncer en regular el creixement tumoral, la invasi\u00f3 i la met\u00e0stasi. No obstant aix\u00f2, els mecanismes subjacents encara es desconeixen en gran manera. La ra\u00f3 principal \u00e9s la falta d’una tecnologia que ens permeti visualitzar qu\u00e8 passa dins del nucli quan est\u00e0 subjecte a una for\u00e7a mec\u00e0nica\u201d, comenta Pere Roca-Cusachs, investigador principal a l\u2019IBEC i professor agregat a la Universitat de Barcelona.<\/p>\n

En aquest treball, els investigadors han identificat recentment un mecanisme subjacent a la mecanotransducci\u00f3 nuclear, mostrant com l’aplicaci\u00f3 de forces f\u00edsiques al nucli afecta al transport de prote\u00efnes a trav\u00e9s de la membrana nuclear i la distribuci\u00f3 resultant entre el citoplasma i el nucli.<\/p>\n

\u201c\u00c9s ben sabut que les forces mec\u00e0niques afecten l’expressi\u00f3 g\u00e8nica. El nostre treball revela un mecanisme que explica com ocorre aix\u00f2\u201d, expliquen I\u00f3 Andreu (coautor principal) i Ignasi Granero (coautor principal).<\/p>\n

Aquest treball s’ha realitzat en col\u00b7laboraci\u00f3 amb el grup de modelatge te\u00f2ric de Barak Raveh (Universitat Hebrea de Jerusalem) i el Francis Crick Institute.<\/p>\n

For\u00e7ar el moviment de prote\u00efnes <\/strong><\/p>\n

Les prote\u00efnes viatgen del nucli al citoplasma, i viceversa, a trav\u00e9s d’estructures espec\u00edfiques denominades Complexos de Porus Nuclears (NPCs) principalment de dues maneres: difusi\u00f3 activa i passiva. El transport passiu \u00e9s r\u00e0pid per a prote\u00efnes petites, per\u00f2 es redueix progressivament a mesura que augmenta el pes molecular de la prote\u00efna. El transport actiu de mol\u00e8cules m\u00e9s grans dep\u00e8n dels receptors de transport nuclear que interactuen amb ells unint-se a seq\u00fc\u00e8ncies espec\u00edfiques, conegudes com a Senyals de Localitzaci\u00f3 Nuclear (NLS, per a prote\u00efnes que entren en el nucli) o Senyals d’Exportaci\u00f3 Nuclear (NES, per a prote\u00efnes que surten del nucli).<\/p>\n

Els autors van trobar que l’aplicaci\u00f3 de forces f\u00edsiques al nucli millora la permeabilitat a trav\u00e9s dels NPCs, la qual cosa augmenta el transport de mol\u00e8cules. A m\u00e9s, van trobar que el transport actiu augmenta m\u00e9s que la difusi\u00f3 passiva. Aquesta resposta diferencial condueix a canvis en el transport de mol\u00e8cules a trav\u00e9s de NPCs en funci\u00f3 de la for\u00e7a.<\/p>\n

Els autors van dissenyar mol\u00e8cules mecanosensibles ajustant la seva difusi\u00f3 passiva a trav\u00e9s de NPCs (canviant el seu pes molecular) i el seu transport actiu (introduint seq\u00fc\u00e8ncies espec\u00edfiques de NLS o NES). En incloure un marcador fluorescent en aquestes mol\u00e8cules, van generar indicadors fluorescents que entren o surten del nucli en resposta a for\u00e7a.<\/p>\n

El potencial terap\u00e8utic de la mecanotransducci\u00f3<\/strong><\/p>\n

 <\/strong>Mitjan\u00e7ant l’optimitzaci\u00f3 i combinaci\u00f3 adequada d’aquestes mol\u00e8cules, els grups liderats per Pere Roca-Cusachs i Xavier Trepat de l’IBEC pretenen desenvolupar sensors emissors de llum que mesurin la mecanotransducci\u00f3 nuclear mitjan\u00e7ant el seguiment de la seva localitzaci\u00f3 nuclear. Aquest treball s’emmarca en un ambici\u00f3s projecte finan\u00e7at per la Convocat\u00f2ria CaixaResearch de Recerca en Salut de la Fundaci\u00f3 \u201cla Caixa\u201d.<\/p>\n

Per a calibrar i validar els sensors, els investigadors utilitzaran posteriorment models animals de c\u00e0ncer de mama i colorectal. Introduiran els sensors en c\u00e8l\u00b7lules canceroses tant d’aquests teixits com de ratolins, i seguiran el seu comportament utilitzant t\u00e8cniques de microsc\u00f2pia avan\u00e7ades. D’aquesta manera, podran seguir la mecanotransducci\u00f3 durant la invasi\u00f3 i met\u00e0stasi del c\u00e0ncer.<\/p>\n

Aquest treball estableix un marc nou per a comprendre com la mec\u00e0nica impulsa la progressi\u00f3 del c\u00e0ncer, obrint la porta a noves t\u00e8cniques potencials tant diagn\u00f2stiques com terap\u00e8utiques.<\/p>\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<\/i> (2022). https:\/\/doi.org\/10.1038\/s41556-022-00927-7<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Un estudi liderat per investigadors de l’IBEC i publicat a la revista Nature Cell Biology demostra que l’aplicaci\u00f3 de for\u00e7a mec\u00e0nica al nucli cel\u00b7lular afecta al transport de prote\u00efnes a trav\u00e9s de la membrana nuclear. Aquesta acci\u00f3 controla els processos cel\u00b7lulars i podria exercir un paper clau en diverses malalties, com el c\u00e0ncer. Aix\u00f2 implica un enfocament nou per a comprendre els aspectes de la invasi\u00f3 del c\u00e0ncer i la met\u00e0stasi, obrint portes a noves t\u00e8cniques potencials tant diagn\u00f2stiques com terap\u00e8utiques.<\/H3><\/p>\n","protected":false},"author":4,"featured_media":95471,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[1722,1134],"post_formats":[],"class_list":["post-94930","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca","tag-mechanotransduccio","tag-pere-roca-cusachs-ca"],"yoast_head":"\nMecanotransducci\u00f3: aplicaci\u00f3 de la mec\u00e0nica nuclear per a comprendre la salut i la malaltia - 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\/ca\/mechanosensing-harnessing-nuclear-mechanics-to-understand-health-and-disease\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Mecanotransducci\u00f3: aplicaci\u00f3 de la mec\u00e0nica nuclear per a comprendre la salut i la malaltia - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Un estudi liderat per investigadors de l'IBEC i publicat a la revista Nature Cell Biology demostra que l'aplicaci\u00f3 de for\u00e7a mec\u00e0nica al nucli cel\u00b7lular afecta al transport de prote\u00efnes a trav\u00e9s de la membrana nuclear. 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