161 research outputs found
Durotaxis
No full textIn this Primer, Sunyer and Trepat introduce durotaxis, the mode of migration by which cells follow gradients of extracellular matrix stiffness
Study of collective cell durotaxis as an active wetting phenomenon
No full text[eng] Cell migration is essential to many biological processes. In adult organisms, it is crucial for wound healing, homeostasis, and immune response, whereas aberrant cell migration potentially leads to pathology. For example, the onset of cell migration in cancer cells can lead to metastasis, where cancer cells escape from the primary tumour confinement, intravasate the blood vessels and circulate through the bloodstream to ultimately extravasate and colonize distant organs. In the context of development, processes such as morphogenesis and organogenesis occur because of cell migration: for an embryo to become an adult organism, cells migrate either as single cells or epithelial sheets to give rise to functional organs and recurrent tissue shapes in a very well-orchestrated and reproducible manner both in time and space. Given its relevance, the regulation mechanisms underlying cell locomotion are highly controlled both at a transcriptional, protein localization and functional level.
The study of cell migration from a biological perspective provided scientists with knowledge on key molecules, effector proteins and signalling pathways that play a crucial role during this process. However, with the emergence of the field of mechanobiology, the fact that physical parameters were no longer neglected shed light on the mechanics behind cell locomotion and enabled us to convey a more accurate idea of this extremely complex process. That is mainly because no matter which signalling cascade is triggered by whatever myriad of protein-ligand interaction driving cell migration, the end-result is a cell or a collective of cells translocating their bulk to a position different than the original one. Therefore, the simplest consideration of cell migration is a physical phenomenon where cells must be subjected to the most basic laws of physics. Consequently, to fully understand the complexities of cell migration, its study must be tackled both from the molecular biology and physical point of view.
In the introduction of this thesis, I will cover the mechanisms regulating cell migration from the molecular to the tissue level, focusing on collective cell migration and durotaxis, the ability of single cells and groups to follow mechanical cues. Next, I will review previous work tackling tissue spreading and migration as a wetting phenomenon, emphasizing on the active gel theory. Finally, although cell migration has been primarily studied when mediated by focal adhesions at the extracellular matrix (ECM) interface, important migratory processes during development or metastasis take place in contexts lacking ECM. Recent studies suggest that E-cadherin, a cell-cell adhesion protein essential to maintain tissue integrity, promote coordination and establish cell polarity, could govern cell migration in ECM-depleted environments. In the last section of this thesis, I will comment on the scarce cadherin-dependent cell migration events published to date, discussing the emerging role of E-cadherin inmediating cell migration
Biophysical characterization of tubulin tyrosine ligase-like proteins on microtubule dynamics
No full textReport for the scientific sojourn carried out at the Cell Biology and Biophysics Unit from the National Institutes of Health, from 2010 to 2012
The Forces behind Directed Cell Migration
No full textDirected cell migration is an essential building block of life, present when an embryo develops, a dendritic cell migrates toward a lymphatic vessel, or a fibrotic organ fails to restore its normal parenchyma. Directed cell migration is often guided by spatial gradients in a physicochemical property of the cell microenvironment, such as a gradient in chemical factors dissolved in the medium or a gradient in the mechanical properties of the substrate. Single cells and tissues sense these gradients, establish a back-to-front polarity, and coordinate the migration machinery accordingly. Central to these steps we find physical forces. In some cases, these forces are integrated into the gradient sensing mechanism. Other times, they transmit information through cells and tissues to coordinate a collective response. At any time, they participate in the cellular migratory system. In this review, we explore the role of physical forces in gradient sensing, polarization, and coordinating movement from single cells to multicellular collectives. We use the framework proposed by the molecular clutch model and explore to what extent asymmetries in the different elements of the clutch can lead to directional migration
Mechanobiology of single cell migration on patterned fibronectin gradients
No full text[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
Study of collective cell durotaxis as an active wetting phenomenon
No full text[eng] Cell migration is essential to many biological processes. In adult organisms, it is crucial for wound healing, homeostasis, and immune response, whereas aberrant cell migration potentially leads to pathology. For example, the onset of cell migration in cancer cells can lead to metastasis, where cancer cells escape from the primary tumour confinement, intravasate the blood vessels and circulate through the bloodstream to ultimately extravasate and colonize distant organs. In the context of development, processes such as morphogenesis and organogenesis occur because of cell migration: for an embryo to become an adult organism, cells migrate either as single cells or epithelial sheets to give rise to functional organs and recurrent tissue shapes in a very well-orchestrated and reproducible manner both in time and space. Given its relevance, the regulation mechanisms underlying cell locomotion are highly controlled both at a transcriptional, protein localization and functional level.
The study of cell migration from a biological perspective provided scientists with knowledge on key molecules, effector proteins and signalling pathways that play a crucial role during this process. However, with the emergence of the field of mechanobiology, the fact that physical parameters were no longer neglected shed light on the mechanics behind cell locomotion and enabled us to convey a more accurate idea of this extremely complex process. That is mainly because no matter which signalling cascade is triggered by whatever myriad of protein-ligand interaction driving cell migration, the end-result is a cell or a collective of cells translocating their bulk to a position different than the original one. Therefore, the simplest consideration of cell migration is a physical phenomenon where cells must be subjected to the most basic laws of physics. Consequently, to fully understand the complexities of cell migration, its study must be tackled both from the molecular biology and physical point of view.
In the introduction of this thesis, I will cover the mechanisms regulating cell migration from the molecular to the tissue level, focusing on collective cell migration and durotaxis, the ability of single cells and groups to follow mechanical cues. Next, I will review previous work tackling tissue spreading and migration as a wetting phenomenon, emphasizing on the active gel theory. Finally, although cell migration has been primarily studied when mediated by focal adhesions at the extracellular matrix (ECM) interface, important migratory processes during development or metastasis take place in contexts lacking ECM. Recent studies suggest that E-cadherin, a cell-cell adhesion protein essential to maintain tissue integrity, promote coordination and establish cell polarity, could govern cell migration in ECM-depleted environments. In the last section of this thesis, I will comment on the scarce cadherin-dependent cell migration events published to date, discussing the emerging role of E-cadherin inmediating cell migration
Rigidity sensing and adaptation through regulation of integrin types
No full textPublished in final edited form as:
Nat Mater. 2014 June ; 13(6): 631–637. http://dx.doi.org/10.1038/nmat396
Mechanobiology of single cell migration on patterned fibronectin gradients
No full textPrograma de Doctorat en Biomedicina / Tesi realitzada a l'Institut de Bioenginyeria de Catalunya (IBEC)[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
Two remarks on the set of recurrent vectors
No full text[EN] We solve in the negative two open problems, related to the linear and topological structure of the set of recurrent vectors, asked by Sophie Grivaux, Alfred Peris and the first author of this paper. Firstly, we show that there exist recurrent operators whose set of recurrent vectors is not dense lineable; and secondly, we construct operators which are reiteratively recurrent and cyclic, but whose set of reiteratively recurrent vectors is meager. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.The first author was supported by the Spanish Ministerio de Ciencia, Innovacion y Universidades, grant FPU2019/04094; by MCIN/AEI/10.13039/501100011033, Projects PID2019-105011GB-I00 and PID2022-139449NB-I00; and by the "Fundacio Ferran Sunyer i Balaguer". The second author is a Research Associate of the Fonds de la Recherche Scientifique - FNRS.López-Martínez, A.; Menet, Q. (2025). Two remarks on the set of recurrent vectors. Journal of Mathematical Analysis and Applications. 541(1). https://doi.org/10.1016/j.jmaa.2024.128686S541
Fabrication of Hydrogels with Gradient of Compliance: Application to Cell Mechanotaxis and Durotaxis
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