{"id":86102,"date":"2021-07-14T12:04:01","date_gmt":"2021-07-14T10:04:01","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/?p=86102"},"modified":"2021-07-15T08:53:29","modified_gmt":"2021-07-15T06:53:29","slug":"lestira-i-arronsa-cel%c2%b7lular-clau-en-la-resposta-de-lorganisme-en-processos-com-el-cancer","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/lestira-i-arronsa-cel%c2%b7lular-clau-en-la-resposta-de-lorganisme-en-processos-com-el-cancer\/","title":{"rendered":"L’estira-i-arronsa cel\u00b7lular, clau en la resposta de l’organisme en processos com el c\u00e0ncer"},"content":{"rendered":"

Des de les cordes vocals que produeixen la nostra veu fins als batecs del cor, les c\u00e8l\u00b7lules del nostre cos estan\u00a0<\/span>sotmeses a forces mec\u00e0niques que canvien constan<\/span>tment la seva resposta a aquests est\u00edmuls, regulant processos essencials, tant en individus sans, com en condicions de malaltia com el c\u00e0ncer.\u00a0<\/span>M<\/span>algrat la seva import\u00e0ncia, continuem desconeixent\u00a0<\/span>malauradament\u00a0<\/span>en gran mesura com les c\u00e8l\u00b7lules perceben i responen\u00a0<\/span>a aquestes forces.<\/span><\/span>\u00a0<\/span><\/p>\n

\"\"<\/p>\n

Ara, un equip internacional\u00a0<\/span>coliderat<\/span>\u00a0pels investigadors Pere Roca-<\/span>Cusachs<\/span>, de l’Institut de Bioenginyeria de Catalunya (IBEC), i Isaac\u00a0<\/span>Almendros<\/span>, investigador del CIBER de Malalties Respirat\u00f2ries (CIBERES) i de\u00a0<\/span>l’IDI<\/span>B<\/span>A<\/span>P<\/span>S<\/span>, tots dos prof<\/span>essors de la Facultat de Medicina<\/span>\u00a0i Ci\u00e8ncies de la Salut<\/span>\u00a0de la Universitat de Barcelona, ha demostrat que el que determina la sensibilitat mec\u00e0nica a les c\u00e8l\u00b7lules \u00e9s el ritme d’aplicaci\u00f3 de la for\u00e7a, \u00e9s a dir, com de r\u00e0pid\u00a0<\/span>s’aplica\u00a0<\/span><\/span>aquesta for\u00e7a<\/span>. El treball s’ha publicat a la p<\/span><\/span>restigiosa revista\u00a0<\/span><\/span>Nature<\/span>\u00a0Communications<\/span><\/span>\u00a0i demostra, per primer cop\u00a0<\/span><\/span>in\u00a0<\/span>vivo<\/span><\/span>, les prediccions del model conegut com a \u201cmolecular\u00a0<\/span>clutch<\/span>\u201d o \u201cembragatge molecular\u201d.<\/span><\/span>\u00a0<\/span>
\n<\/span>Aquests resultats, <\/span>ajudaran a entendre millor<\/span>,\u00a0<\/span>per exemple<\/span>,<\/span>\u00a0com prolifera un tumor cancerigen\u00a0<\/span>o a comprendre com responen el cor, les cordes vocals o el sistema respiratori a la constant variaci\u00f3 de forces a qu\u00e8 s’exposen cont\u00ednuament.<\/span><\/span>\u00a0<\/span><\/p>\n

Imatge 1: <\/strong>Isaac Almendros i Pere Roca-<\/span>Cusachs (d’esquerra a dreta) l\u00edders de la investigaci\u00f3.<\/span><\/h6>\n

Un constant \u201cestira-i-arronsa\u201d cel\u00b7lula<\/span>r<\/span><\/span><\/strong>\u00a0<\/span><\/h2>\n

Els investigadors, gr\u00e0cies a la utilitzaci\u00f3 de t\u00e8cniques capdavanteres com ara la microsc\u00f2pia de for\u00e7a at\u00f2mica (AFM) o les anomenades \u201cpinces \u00f2ptiques\u201d, han observat que hi ha dues respostes a la for\u00e7a aplicada sobre una c\u00e8l\u00b7lula.<\/span>\u00a0<\/span><\/p>\n

Per una banda, el citoesquelet, el dens entramat de fibres (principalment actina), que t\u00e9, entre d’altres, la funci\u00f3 de mantenir la forma i l’estructura de la c\u00e8l\u00b7lula, es refor\u00e7a quan \u00e9s sotm\u00e8s a una for\u00e7a a un ritme moderat. En aquest context, la c\u00e8l\u00b7lula \u00e9s capa\u00e7 de sentir i de respondre a la for\u00e7a mec\u00e0nica, i el refor\u00e7 del citoesquelet du a un enduriment de la c\u00e8l\u00b7lula i a la localitzaci\u00f3 de la prote\u00efna YAP en el nucli. Quan aix\u00f2 succeeix, la prote\u00efna YAP controla i activa gens relacionats amb el desenvolupament del c\u00e0ncer.<\/span>\u00a0<\/span><\/p>\n

D’altra banda, si el ritme d’aplicaci\u00f3 de for\u00e7a continua augmentant per damunt d’un determinat valor, es produeix un efecte contrari i la c\u00e8l\u00b7lula deixa de percebre les forces mec\u00e0niques. \u00c9s a dir, en lloc que el citoesquelet i la c\u00e8l\u00b7lula continu\u00efn augmentant la rigidesa, hi ha una ruptura parcial del citoesquelet que du a un reblaniment de la c\u00e8l\u00b7lula.<\/span>\u00a0<\/span><\/p>\n

Com qui estira i arronsa un xiclet, hem sotm\u00e8s les c\u00e8l\u00b7lules a diferents forces de manera controlada i precisa, i hem vist que el ritme amb qu\u00e8 s’aplica l<\/span>a for\u00e7a \u00e9s crucial per determinar la resposta cel\u00b7lular.<\/span><\/strong><\/p>\n

Ion<\/span>\u00a0Andreu (IBEC), coautor principal de l’estudi<\/span><\/span>\u00a0<\/span> <\/strong><\/p>\n<\/blockquote>\n

Un model corroborat amb experiments\u00a0<\/span><\/span>in\u00a0<\/span>vivo<\/span><\/span>\u00a0<\/span><\/em><\/strong><\/h2>\n

Per entendre com es relacionen els efectes d’esfor\u00e7 i reblaniment del citoesquelet, els investigadors v<\/span>an desenvolupar un model computacional que considera l’efecte de l’aplicaci\u00f3 progressiva de for\u00e7a sobre el citoesquelet i els \u201cenganxalls” (prote\u00efnes que participen en la uni\u00f3 de la c\u00e8l\u00b7lula al substrat, com la\u00a0<\/span>talina<\/span>\u00a0i la integrina). Aquests \u201cenganxalls\u201d\u00a0<\/span>s\u00f3n, d’alguna manera, an\u00e0legs a l’efecte que t\u00e9 un embragatge de cotxe en ajustar la connexi\u00f3 mec\u00e0nica entre el motor i les rodes, i per aix\u00f2 el model s’anomena \u201cembragatge molecular\u201d.<\/span><\/span>\u00a0<\/span><\/p>\n

\"\"<\/p>\n

Posteriorment, els cient\u00edfics van realitzar experiments amb rates de l<\/span>aboratori per comprovar que els resultats observats en c\u00e8l\u00b7lules individuals tamb\u00e9 es produeixen a nivell d’\u00f2rgans sencers\u00a0<\/span><\/span>in\u00a0<\/span>vivo<\/span>.<\/span><\/span>\u00a0Per fer-ho, els investigadors es van fixar en els pulmons, que de forma natural experimenten estiraments mec\u00e0nics c\u00edclics du<\/span>rant la respiraci\u00f3. Concretament, es van ventilar els dos pulmons a ritmes diferents, de manera que un pulm\u00f3 s’emplenava i buidava m\u00e9s r\u00e0pid (hiperventilaci\u00f3) i l’altre m\u00e9s a poc a poc, encara que mantenint una taxa total de ventilaci\u00f3 normal.<\/span><\/span>
\n<\/span>Despr\u00e9s d’a<\/span>nalitzar i comparar les c\u00e8l\u00b7lules de tots dos pulmons, van observar que la prote\u00efna YAP augmentava la seva localitzaci\u00f3 nuclear nom\u00e9s a les c\u00e8l\u00b7lules del pulm\u00f3 sotm\u00e8s a una hiperventilaci\u00f3.\u00a0<\/span><\/span>Aquest augment de YAP en mostres vives, causat per\u00a0<\/span>l’\u201cestira<\/span>-i-arr<\/span>onsa cel\u00b7lular\u201d, era an\u00e0leg al que es troba a tumors cancer\u00edgens en proliferaci\u00f3.<\/span><\/span>\u00a0<\/span><\/strong><\/p>\n

Imatge 2.<\/strong>Pulm\u00f3 de rata que respon a la ventilaci\u00f3 amb tinci\u00f3 de prote\u00efnes YAP.<\/h6>\n

Els nostres resultats demostren, pel que fa a l’\u00f2rgan, el paper del ritme d’aplicaci\u00f3 de la for\u00e7a en la transducci\u00f3 del senyal mec\u00e0nic indu\u00eft per ventilaci\u00f3 en els pulmons.<\/span><\/span> <\/strong><\/p>\n

Bryan\u00a0<\/span>Falcones<\/span>\u00a0(IBEC-UB), coautor principal de l’estudi<\/span><\/span>\u00a0<\/span><\/strong><\/p>\n

\u00a0<\/strong><\/p><\/blockquote>\n

El treball descriu un mecanisme pel qual les c\u00e8l\u00b7lules responen no nom\u00e9s a forces directes, sin\u00f3 tamb\u00e9 a altres est\u00edmuls mec\u00e0nics passius, com ara la rigidesa del substrat en qu\u00e8 es troben. Els resultats obren la porta a entendre com fen\u00f2mens\u00a0<\/span><\/span>a priori<\/span><\/span>\u00a0opos<\/span>ats, com ara el refor\u00e7 i el reblaniment del citoesquelet, poden\u00a0<\/span>combinar-se<\/span>\u00a0<\/span>per controlar la mec\u00e0nica de la c\u00e8l\u00b7lula, i respondre espec\u00edficament<\/span>,<\/span>\u00a0a diferents situacions.<\/span><\/span>\u00a0<\/span><\/p>\n

\n
\n

Article de refer\u00e8ncia:<\/span><\/span>\u00a0<\/span><\/strong><\/p>\n

Ion Andreu, Bryan\u00a0Falcones, Sebastian Hurst,\u00a0Nimesh\u00a0Chahare,\u00a0Xarxa\u00a0Quiroga, Anabel-Lise Le Roux,\u00a0Zanetta\u00a0Kechagia, Amy E. M. Beedle, Alberto\u00a0El\u00f3segui-Artola, Xavier Trepat, Ramon\u00a0Farr\u00e9, Timo Betz, Isaac Almendros & Pere Roca-Cusachs.\u00a0<\/span>The force loading rate drives cell\u00a0mechanosensing\u00a0through both reinforcement and\u00a0cytoskeletal softening<\/strong>.<\/strong> Nature Communications, 2021.<\/span>\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Investigadors liderats per Pere Roca-Cusachs a l’Institut de Bioenginyeria de Catalunya (IBEC) descobreixen com la din\u00e0mica de forces afecta les c\u00e8l\u00b7lules i els teixits vius. Els resultats ajuden a entendre els processos mec\u00e0nics crucials que es duen a terme en diferents malalties, com ara el c\u00e0ncer.<\/h3>\n","protected":false},"author":4,"featured_media":86099,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[1522,1134],"post_formats":[],"class_list":["post-86102","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca","tag-ciber","tag-pere-roca-cusachs-ca"],"yoast_head":"\nL'estira-i-arronsa cel\u00b7lular, clau en la resposta de l'organisme en processos com el c\u00e0ncer - 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\/lestira-i-arronsa-cel\u00b7lular-clau-en-la-resposta-de-lorganisme-en-processos-com-el-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"L'estira-i-arronsa cel\u00b7lular, clau en la resposta de l'organisme en processos com el c\u00e0ncer - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Investigadors liderats per Pere Roca-Cusachs a l'Institut de Bioenginyeria de Catalunya (IBEC) descobreixen com la din\u00e0mica de forces afecta les c\u00e8l\u00b7lules i els teixits vius. 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