{"id":65371,"date":"2019-01-23T10:21:06","date_gmt":"2019-01-23T09:21:06","guid":{"rendered":"http:\/\/ibecbarcelona.eu\/large-scale-curvature-sensing-by-directional-actin-flow-drives-cellular-migration-mode-switching\/"},"modified":"2019-01-24T15:43:02","modified_gmt":"2019-01-24T14:43:02","slug":"large-scale-curvature-sensing-by-directional-actin-flow-drives-cellular-migration-mode-switching","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/large-scale-curvature-sensing-by-directional-actin-flow-drives-cellular-migration-mode-switching\/","title":{"rendered":"Nou avan\u00e7 en el coneixement sobre el canvi de flux d’actina en la migraci\u00f3 cel\u00b7lular"},"content":{"rendered":"

Per una banda, el creixement i extensi\u00f3 de protrusions lamel\u00b7lipodials \u00a0de pol\u00edmers d\u2019actina que permeten a la c\u00e8l\u00b7lula \u201crastrejar” cap a l’exterior, i de l\u2019altra banda la formaci\u00f3 de grans cables contr\u00e0ctils d\u2019actomiosina que poden estirar cap endavant la c\u00e8l\u00b7lula mentre generen forces de tracci\u00f3 sobre el substrat. Tanmateix, el proc\u00e9s pel qual la c\u00e8l\u00b7lula decideix formar protrusions o cables contr\u00e0ctils encara no est\u00e0 clar.<\/p>\n

Depenent de la tipografia de l\u2019entorn f\u00edsic, les c\u00e8l\u00b7lules poden trobar-se regions amb curvatura positiva o negativa. La curvatura positiva es refereix a la forma convexa que corba cap a l\u2019exterior, en forma de D maj\u00fascula, mentre que la curvatura negativa adopta la forma de lletra ‘C’, \u00a0una corba c\u00f2ncava cap a l’interior. En observar la migraci\u00f3 cel\u00b7lular epitelial en patrons de substrat en forma de flor, que s’utilitzen per a assaigs de tancament de ferides, un grup de recerca liderat per MBI Visiting Faculti Prof. Benoit Ladoux en col\u00b7laboraci\u00f3 amb MBI PIs BC. Low, Y. Toyama, el f\u00edsic te\u00f2ric R. Voituriez, A. Callan-Jones i T. Shemesh juntament amb l\u2019investigador principal de l\u2019IBEC Xavier Trepat han descobert que a les regions amb curvatura positiva, les c\u00e8l\u00b7lules han desenvolupat lamel\u00b7lipodia per al rastreig de c\u00e8l\u00b7lules, i en regions de curvatura negativa, forts cables d’actina acoblats a la vora c\u00f2ncava.<\/p>\n

Dirigint el flux d\u2019actina<\/h3>\n

Observacions addicionals de la din\u00e0mica de l’actina en temps real, mitjan\u00e7ant microsc\u00f2pia de c\u00e8l\u00b7lules vives, van revelar una difer\u00e8ncia en la direcci\u00f3 del flux d’actina en les dues curvatures. En la curvatura positiva indu\u00efda per lamel\u00b7lipodia, el flux d\u2019actina era retr\u00f2grad, \u00e9s a dir, lluny de la membrana cel\u00b7lular en la direcci\u00f3 oposada a la protrusi\u00f3. Per contra, a curvatures negatives, el flux d’actina era anter\u00f2grad, \u00e9s a dir, cap a la membrana cel\u00b7lular on es localitzava el cable de l’actina. Aquest flux anter\u00f2grad acciona l\u2019acoblament de diferents estructures d’actina polaritzada en aquestes regions de curvatura negativa. El cable d\u2019actina de la vora c\u00f2ncava est\u00e0 localitzada a la part frontal, seguida de fibres d\u2019actina transversals orientades en la mateixa direcci\u00f3 que el cable d\u2019actina, i al\u00e7ant la part posterior de la xarxa, s\u00f3n fibres d’actina radial orientades a 90 graus al cable d\u2019actina. Curiosament, la formaci\u00f3 d’aquestes estructures d’actina polaritzada en resposta a la curvatura negativa, es va observar en c\u00e8l\u00b7lules simples i fulls cel\u00b7lulars que migren en una superf\u00edcie 2D i en c\u00e8l\u00b7lules incrustades en xarxes fibroses 3D. Tot i que aquests resultats confirmen l’exist\u00e8ncia de dos mecanismes de migraci\u00f3 cel\u00b7lular, encara \u00e9s una pregunta oberta sobre com les c\u00e8l\u00b7lules s\u00f3n capaces de sentir la curvatura de l\u2019entorn.<\/p>\n

Afortunadament, les imatges de c\u00e8l\u00b7lules en viu subministrades pels investigadors donen una pista potencial \u2013 el canvi en la direcci\u00f3 del flux d\u2019actina que dep\u00e8n de la curvatura, pot ser potencialment el “sensor” que canvia el mode de migraci\u00f3. Aix\u00f2 es va confirmar plantant c\u00e8l\u00b7lules epitelials sobre una superf\u00edcie micro-modelada recoberta amb un substrat adhesiu, que va ser dotat de pegats circulars no adherents. Quan el full de c\u00e8l\u00b7lules troba un cercle no adherent, les protrusions lamel\u00b7l\u00edpodes s’arrosseguen al voltant del cercle, estirant les c\u00e8l\u00b7lules cap endavant sobre el substrat adhesiu. Aix\u00f2 provoca una forma c\u00f2ncava a trav\u00e9s del cercle no adherent, el qual causa un canvi r\u00e0pid en la direcci\u00f3 del flux d\u2019actomiosina de retr\u00f2grad a anter\u00f2grad, i d\u00f3na com a resultat l\u2019assemblatge del cable d\u2019actina i un canvi en el mecanisme de migraci\u00f3. El cable contr\u00e0ctil pot aixecar la vora de la c\u00e8l\u00b7lula per sobre del cercle no adherent, permetent que la migraci\u00f3 cel\u00b7lular continu\u00ef.<\/p>\n

Aix\u00ed com les c\u00e8l\u00b7lules contenen sensors de curvatura en la seva membrana, com per exemple les prote\u00efnes BAR, aquests nom\u00e9s permeten detectar la curvatura a escala molecular. Essencialment, la mida d\u2019aquestes prote\u00efnes-sensor significa que tan sols poden sentir la curvatura en la seva immediata proximitat a una escala de nanom\u00e8trica, no a nivell cel\u00b7lular. Malgrat aix\u00f2, \u00a0aquest estudi revela com les c\u00e8l\u00b7lules poden detectar canvis en la curvatura en mides superiors a l\u2019escala cel\u00b7lular a una escala de fins a desenes de micres, a trav\u00e9s de l’adaptaci\u00f3 din\u00e0mica del flux d’actina. Aquesta habilitat permet a la c\u00e8l\u00b7lula seleccionar el mecanisme apropiat per continuar la migraci\u00f3, incl\u00fas quan han de fer front a diversos canvis de l\u2019entorn f\u00edsic. Amb aquest nou coneixement sobre el canvi de flux d’actina, els cient\u00edfics poden ser m\u00e9s capa\u00e7os d’entendre com les c\u00e8l\u00b7lules poden continuar la migraci\u00f3 durant la cicatritzaci\u00f3 d\u2019una ferida o en situacions en qu\u00e8 la migraci\u00f3 pot ser perjudicial, com la progressi\u00f3 metast\u00e0tica del c\u00e0ncer.<\/p>\n

\u2014<\/p>\n

Tianchi Chen, Andrew Callan-Jones, Eduard Fedorov, Andrea Ravasio, Agust\u00ed Brugu\u00e9s, Hui Ting Ong, Yusuke Toyama, Boon Chuan Low, Xavier Trepat, Tom Shemesh, Rapha\u00ebl Voituriez & Beno\u00eet Ladoux (2019).\u00a0Large-scale curvature sensing by directional actin flow drives cellular migration mode switching<\/a>.\u00a0Nature Physics.\u00a0<\/i>DOI:\u00a010.1038\/s41567-018-0383-6<\/p>\n","protected":false},"excerpt":{"rendered":"

La migraci\u00f3 cel\u00b7lular \u00e9s un proc\u00e9s biol\u00f2gic essencial que condueix la formaci\u00f3 de teixits i \u00f2rgans durant el desenvolupament embrional que tamb\u00e9 ajuda a protegir el cos a trav\u00e9s de la resposta immunit\u00e0ria i els mecanismes de cicatritzaci\u00f3 de ferides. Els canvis en la forma necessaris per a la migraci\u00f3 cel\u00b7lular dep\u00e8n de l\u2019organitzaci\u00f3 din\u00e0mica i la generaci\u00f3 de forces del citoesquelet d\u2019actomiosina intern de la c\u00e8l\u00b7lula, que est\u00e0 format per filaments d\u2019actina estructurals y prote\u00efnes motores contr\u00e0ctils de miosina.<\/h3>\n

La reorganitzaci\u00f3 d\u2019aquests components permet dos mecanismes de migraci\u00f3 cel\u00b7lular.
\n\"\"<\/p>\n","protected":false},"author":4,"featured_media":65363,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[437,436],"post_formats":[],"class_list":["post-65371","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca","tag-cellular-motility-ca","tag-migracio-cellular"],"yoast_head":"\nNou avan\u00e7 en el coneixement sobre el canvi de flux d'actina en la migraci\u00f3 cel\u00b7lular - 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\/large-scale-curvature-sensing-by-directional-actin-flow-drives-cellular-migration-mode-switching\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Nou avan\u00e7 en el coneixement sobre el canvi de flux d'actina en la migraci\u00f3 cel\u00b7lular - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"La migraci\u00f3 cel\u00b7lular \u00e9s un proc\u00e9s biol\u00f2gic essencial que condueix la formaci\u00f3 de teixits i \u00f2rgans durant el desenvolupament embrional que tamb\u00e9 ajuda a protegir el cos a trav\u00e9s de la resposta immunit\u00e0ria i els mecanismes de cicatritzaci\u00f3 de ferides. 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