Mechanobiology of single cell migration on patterned fibronectin gradients

[eng] Directed cell migration along gradients of extracellular matrix (ECM) density – a process called haptotaxis – plays a central role in morphogenesis, the immune response, and cancer invasion. It is commonly assumed that cells respond to these gradients by migrating directionally towards the reg...

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Detalles Bibliográficos
Autor: Fortunato, Isabela Corina Santos
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/218962
Acceso en línea:https://hdl.handle.net/2445/218962
http://hdl.handle.net/10803/693724
Access Level:acceso abierto
Palabra clave:Migració cel·lular
Matriu extracel·lular
Cell migration
Extracellular matrix
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spelling Mechanobiology of single cell migration on patterned fibronectin gradientsFortunato, Isabela Corina SantosMigració cel·lularMatriu extracel·lularCell migrationExtracellular matrix[eng] Directed cell migration along gradients of extracellular matrix (ECM) density – a process called haptotaxis – plays a central role in morphogenesis, the immune response, and cancer invasion. It is commonly assumed that cells respond to these gradients by migrating directionally towards the regions of highest ligand density. In contrast with this view, here we show that the integration of ECM gradient sensing and persistent polarity dynamics can give rise to non-trivial migration trajectories, including migration against the gradient and persistent circles. We generated symmetric patterns of fibronectin density confined to rectangular areas of different width. As expected, upon adhering to these patterns, cells polarized and migrated robustly towards the direction of the highest protein density. However, after reaching the maximal density, cells exhibited different migration patterns depending on the gradient width. On confined 1D gradients, cells failed to repolarize and continued to migrate persistently against the fibronectin gradient. By contrast, on wide gradients, they made a 90º turn and migrated along the ridge defined by the maximal fibronectin density. For intermediate widths, non-trivial trajectories such as circles emerged. Overall, our study reveals that confinement modulates the ability of cells to sense and respond to haptotactic cues and provides a framework to understand how cells navigate complex and dynamic environments.[cat] La migració cel·lular dirigida al llarg dels gradients de densitat de la matriu extracel·lular (ECM) – un procés anomenat haptotaxi – té un paper central en la morfogènesi, la resposta immune i la invasió del càncer. Se suposa habitualment que les cèl·lules responen a aquests gradients migrant direccionalment cap a les regions de major densitat de lligands. En contrast amb aquesta visió, aquí mostrem que la integració de la detecció del gradient ECM i la dinàmica de polaritat persistent pot donar lloc a trajectòries de migració no trivials, inclosa la migració contra el gradient i els cercles persistents. Hem generat patrons simètrics de densitat de fibronectina confinats a àrees rectangulars de diferent amplada. Com era d'esperar, en adherir-se a aquests patrons, les cèl·lules es van polaritzar i van migrar amb força cap a la direcció de la densitat de proteïnes més alta. Tanmateix, després d'assolir la densitat màxima, les cèl·lules van mostrar diferents patrons de migració en funció de l'amplada del gradient. En gradients 1D confinats, les cèl·lules no es van repolaritzar i van continuar migrant de manera persistent contra el gradient de fibronectina. En canvi, en gradients amplis, van fer un gir de 90º i van migrar per la carena definida per la densitat màxima de fibronectina. Per a amplades intermèdies, van sorgir trajectòries no trivials com els cercles. En general, el nostre estudi revela que el confinament modula la capacitat de les cèl·lules per detectar i respondre a senyals haptotàctiques i proporciona un marc per entendre com les cèl·lules naveguen per entorns complexos i dinàmics.Universitat de BarcelonaTrepat Guixer, XavierSunyer, RaimonUniversitat de Barcelona. Facultat de Medicina i Ciències de la Salut2024info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/218962http://hdl.handle.net/10803/693724Tesis Doctorals - Facultat - Medicina i Ciències de la Salutreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaIngléscc by-nc-nd (c) Fortunato, Isabela Corina Santos, 2025info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2189622026-05-27T06:46:51Z
dc.title.none.fl_str_mv Mechanobiology of single cell migration on patterned fibronectin gradients
title Mechanobiology of single cell migration on patterned fibronectin gradients
spellingShingle Mechanobiology of single cell migration on patterned fibronectin gradients
Fortunato, Isabela Corina Santos
Migració cel·lular
Matriu extracel·lular
Cell migration
Extracellular matrix
title_short Mechanobiology of single cell migration on patterned fibronectin gradients
title_full Mechanobiology of single cell migration on patterned fibronectin gradients
title_fullStr Mechanobiology of single cell migration on patterned fibronectin gradients
title_full_unstemmed Mechanobiology of single cell migration on patterned fibronectin gradients
title_sort Mechanobiology of single cell migration on patterned fibronectin gradients
dc.creator.none.fl_str_mv Fortunato, Isabela Corina Santos
author Fortunato, Isabela Corina Santos
author_facet Fortunato, Isabela Corina Santos
author_role author
dc.contributor.none.fl_str_mv Trepat Guixer, Xavier
Sunyer, Raimon
Universitat de Barcelona. Facultat de Medicina i Ciències de la Salut
dc.subject.none.fl_str_mv Migració cel·lular
Matriu extracel·lular
Cell migration
Extracellular matrix
topic Migració cel·lular
Matriu extracel·lular
Cell migration
Extracellular matrix
description [eng] Directed cell migration along gradients of extracellular matrix (ECM) density – a process called haptotaxis – plays a central role in morphogenesis, the immune response, and cancer invasion. It is commonly assumed that cells respond to these gradients by migrating directionally towards the regions of highest ligand density. In contrast with this view, here we show that the integration of ECM gradient sensing and persistent polarity dynamics can give rise to non-trivial migration trajectories, including migration against the gradient and persistent circles. We generated symmetric patterns of fibronectin density confined to rectangular areas of different width. As expected, upon adhering to these patterns, cells polarized and migrated robustly towards the direction of the highest protein density. However, after reaching the maximal density, cells exhibited different migration patterns depending on the gradient width. On confined 1D gradients, cells failed to repolarize and continued to migrate persistently against the fibronectin gradient. By contrast, on wide gradients, they made a 90º turn and migrated along the ridge defined by the maximal fibronectin density. For intermediate widths, non-trivial trajectories such as circles emerged. Overall, our study reveals that confinement modulates the ability of cells to sense and respond to haptotactic cues and provides a framework to understand how cells navigate complex and dynamic environments.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/218962
http://hdl.handle.net/10803/693724
url https://hdl.handle.net/2445/218962
http://hdl.handle.net/10803/693724
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv cc by-nc-nd (c) Fortunato, Isabela Corina Santos, 2025
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Fortunato, Isabela Corina Santos, 2025
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Facultat - Medicina i Ciències de la Salut
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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