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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| 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 |
| Sumario: | [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. |
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