Relevant bibliographies by topics / Durotaxie

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  1. Journal articles
  2. Dissertations / Theses
  3. Book chapters
  4. Conference papers

Academic literature on the topic 'Durotaxie'

Author: Grafiati
Published: 7 July 2024

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Journal articles on the topic "Durotaxie"

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Sunyer, Raimon, and Xavier Trepat. "Durotaxis." Current Biology 30, no. 9 (May 2020): R383—R387. http://dx.doi.org/10.1016/j.cub.2020.03.051.

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Huang, Yuxing, Jing Su, Jiayong Liu, Xin Yi, Fang Zhou, Jiaran Zhang, Jiaxiang Wang, Xuan Meng, Lu Si, and Congying Wu. "YAP Activation in Promoting Negative Durotaxis and Acral Melanoma Progression." Cells 11, no. 22 (November 9, 2022): 3543. http://dx.doi.org/10.3390/cells11223543.

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Directed cell migration towards a softer environment is called negative durotaxis. The mechanism and pathological relevance of negative durotaxis in tumor progression still requires in-depth investigation. Here, we report that YAP promotes the negative durotaxis of melanoma. We uncovered that the RhoA-myosin II pathway may underlie the YAP enhanced negative durotaxis of melanoma cells. Acral melanoma is the most common subtype of melanoma in non-Caucasians and tends to develop in a stress-bearing area. We report that acral melanoma patients exhibit YAP amplification and increased YAP activity. We detected a decreasing stiffness gradient from the tumor to the surrounding area in the acral melanoma microenvironment. We further identified that this stiffness gradient could facilitate the negative durotaxis of melanoma cells. Our study advanced the understanding of mechanical force and YAP in acral melanoma and we proposed negative durotaxis as a new mechanism for melanoma dissemination.
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Puleo, Julieann I., Sara S. Parker, Mackenzie R. Roman, Adam W. Watson, Kiarash Rahmani Eliato, Leilei Peng, Kathylynn Saboda, et al. "Mechanosensing during directed cell migration requires dynamic actin polymerization at focal adhesions." Journal of Cell Biology 218, no. 12 (October 8, 2019): 4215–35. http://dx.doi.org/10.1083/jcb.201902101.

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The mechanical properties of a cell’s microenvironment influence many aspects of cellular behavior, including cell migration. Durotaxis, the migration toward increasing matrix stiffness, has been implicated in processes ranging from development to cancer. During durotaxis, mechanical stimulation by matrix rigidity leads to directed migration. Studies suggest that cells sense mechanical stimuli, or mechanosense, through the acto-myosin cytoskeleton at focal adhesions (FAs); however, FA actin cytoskeletal remodeling and its role in mechanosensing are not fully understood. Here, we show that the Ena/VASP family member, Ena/VASP-like (EVL), polymerizes actin at FAs, which promotes cell-matrix adhesion and mechanosensing. Importantly, we show that EVL regulates mechanically directed motility, and that suppression of EVL expression impedes 3D durotactic invasion. We propose a model in which EVL-mediated actin polymerization at FAs promotes mechanosensing and durotaxis by maturing, and thus reinforcing, FAs. These findings establish dynamic FA actin polymerization as a central aspect of mechanosensing and identify EVL as a crucial regulator of this process.
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Style, R. W., Y. Che, S. J. Park, B. M. Weon, J. H. Je, C. Hyland, G. K. German, et al. "Patterning droplets with durotaxis." Proceedings of the National Academy of Sciences 110, no. 31 (June 24, 2013): 12541–44. http://dx.doi.org/10.1073/pnas.1307122110.

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Hartman, Christopher D., Brett C. Isenberg, Samantha G. Chua, and Joyce Y. Wong. "Vascular smooth muscle cell durotaxis depends on extracellular matrix composition." Proceedings of the National Academy of Sciences 113, no. 40 (September 19, 2016): 11190–95. http://dx.doi.org/10.1073/pnas.1611324113.

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Mechanical compliance has been demonstrated to be a key determinant of cell behavior, directing processes such as spreading, migration, and differentiation. Durotaxis, directional migration from softer to more stiff regions of a substrate, has been observed for a variety of cell types. Recent stiffness mapping experiments have shown that local changes in tissue stiffness in disease are often accompanied by an altered ECM composition in vivo. However, the importance of ECM composition in durotaxis has not yet been explored. To address this question, we have developed and characterized a polyacrylamide hydrogel culture platform featuring highly tunable gradients in mechanical stiffness. This feature, together with the ability to control ECM composition, allows us to isolate the effects of mechanical and biological signals on cell migratory behavior. Using this system, we have tracked vascular smooth muscle cell migration in vitro and quantitatively analyzed differences in cell migration as a function of ECM composition. Our results show that vascular smooth muscle cells undergo durotaxis on mechanical gradients coated with fibronectin but not on those coated with laminin. These findings indicate that the composition of the adhesion ligand is a critical determinant of a cell’s migratory response to mechanical gradients.
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Yuehua, YANG, and JIANG Hongyuan. "Research Advances in Cell Durotaxis." 应用数学和力学 42, no. 10 (2021): 999–1007. http://dx.doi.org/10.21656/1000-0887.420265.

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Bueno, Jesus, Yuri Bazilevs, Ruben Juanes, and Hector Gomez. "Wettability control of droplet durotaxis." Soft Matter 14, no. 8 (2018): 1417–26. http://dx.doi.org/10.1039/c7sm01917c.

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Doering, Charles R., Xiaoming Mao, and Leonard M. Sander. "Random walker models for durotaxis." Physical Biology 15, no. 6 (September 11, 2018): 066009. http://dx.doi.org/10.1088/1478-3975/aadc37.

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Stefanoni, Filippo, Maurizio Ventre, Francesco Mollica, and Paolo A. Netti. "A numerical model for durotaxis." Journal of Theoretical Biology 280, no. 1 (July 2011): 150–58. http://dx.doi.org/10.1016/j.jtbi.2011.04.001.

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Parida, Lipika, and Venkat Padmanabhan. "Durotaxis in Nematode Caenorhabditis elegans." Biophysical Journal 111, no. 3 (August 2016): 666–74. http://dx.doi.org/10.1016/j.bpj.2016.06.030.

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Dissertations / Theses on the topic "Durotaxie"

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Tettarasar, Samuel. "Régulation du choix de migration par l’histoire environnementale de la cellule." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASL154.

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Les cellules peuvent migrer de façon aléatoire ou dirigée. La durotaxie est un phénomène de migration dirigée, si les cellules ont le choix, elles vont préférentiellement migrer vers des environnements durs, plutôt que mous. Il a été montré que les cellules pouvaient retenir des informations de leurs environnements passés, ce qui modifie leurs migrations. Ceci est appelé « mémoire mécanique ». Nous avons montré que la mémoire mécanique avait un impact sur la durotaxie des cellules. De plus, nos résultats suggèrent que les cellules sont capables d’associer des stimuli rencontrés dans leur passé, modifiant leurs migrations. Ce phénomène rappelle la mémoire associative qui permet au chien de Pavlov d’anticiper l’arrivée de nourriture en salivant quand il entend le son de la cloche, car ces deux éléments ont été associés dans son passé. De telles capacités d’adaptation associative peuvent apporter un avantage sélectif des cellules cancéreuses dans un environnement qui est complexe
Cells can migrate randomly or in a directed manner. Durotaxis is a phenomenon of directed migration, where if given a choice, cells will preferentially migrate towards hard environments rather than soft ones. It has been shown that cells can retain information from their past environments, which modifies their migration. This is called "mechanical memory". We have shown that mechanical memory has an impact on cell durotaxis. Furthermore, our results suggest that cells are capable of associating stimuli encountered in their past, modifying their migration. This phenomenon is reminiscent of the associative memory that allows Pavlov's dog to anticipate the arrival of food by salivating when it hears the sound of the bell because these two elements have been associated together in its past. Such associative adaptation may provide a selective advantage for cancer cells in a complex environment
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STEFANONI, Filippo. "DUROTAXIS MODELLING FOR TISSUE ENGINEERING APPLICATIONS." Doctoral thesis, Università degli studi di Ferrara, 2010. http://hdl.handle.net/11392/2389166.

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Tissue Engineering is a very promising research field for the development of natural biological substitutes that restore damaged tissue functions. Cells play a crucial role in tissue regeneration and repair due to their characteristics of proliferation and differentiation, cell-to-cell interaction, biomolecular production and extracellular matrix formation. In particular cell migration is a phenomenon that is involved in different physiological processes such as morphogenesis, wound healing and new tissue deposition. In the absence of external guiding factors it is essentially a phenomenon that shares quite a few analogies with Brownian motion. The presence of biochemical or biophysical cues, on the other hand, can influence cell migration in terms of speed, direction and persistence, transforming it in a biased random movement. Recent studies have shown that cells, in particular fibroblasts, are able to recognize the mechanical properties of a substratum over which they move and that these properties direct the motion through a phenomenon called durotaxis. The aim of this thesis is to study this phenomenon for a better understanding of cell behaviour in durotaxis conditions and for Tissue Engineering applications. In order to do that, in the first part of the work a mathematical model for the description of durotaxis is presented. The model is based on a stochastic differential equation for the cell velocity which is derived from the Langevin equation: cell movement is affected by two forces, namely a deterministic one representing the dissipative effects of the system, and a stochastic one which is due to all the probabilistic processes that might affect cell motility (random fluctuations in motile sensing, response mechanisms, etc.). The original contribution of this work concerns the stochastic force, which has been modified to account for the directions of highest perceived local stiffness through a finite element scheme that reminds the cellular probing mechanism. Numerical simulations of the model provide individual cell tracks that can be qualitatively compared with experimental observations. The present model is solved for two important cases that are reported in literature and a comparison with experimental data obtained on PDMS substrata is presented. The degree of agreement is satisfactory thus the model could be utilized to quantify relevant parameters of cell migration as a function of substratum mechanical properties. The second part of the work is concerned on the study and development of a durotaxis-based substratum, able to guide cells in their migration and in particular, able to guide cells along straight path. It was proved, in fact, that a relation exist between the alignment of collagen produced by fibroblasts or others tissue cells and their migration. Thus, the idea is to obtain an aligned tissue made of new collagen, giving to the cells the conditions to move along straight-lines through the mechanical properties of the substratum. To realize this substratum Polyethylenglycole (PEG) was used. First, smooth PEG was synthesized and cell migration experiments was performed over it to better understand its response. Then a specific technique was developed to produce durotaxis-based PEG substrata, and preliminary experiments of cell adhesion over it were performed showing aligned adhesion of cells over them.
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Diego, Íñiguez Javier. "On the theory of cell migration: durotaxis and chemotaxis." Doctoral thesis, Universitat Politècnica de Catalunya, 2013. http://hdl.handle.net/10803/129085.

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Cell migration is a fundamental element in a variety of physiological and pathological processes. Alteration of its regulatory mechanisms leads to loss of adhesion and increased motility, critical steps in the initial stages of metastasis. Consequently, cell migration has become the focus of intensive experimental and theoretical studies; however the understanding many of its mechanisms remains elusive. Cell migration is the result of a periodic sequence of protrusion, adhesion remodeling and contraction stages that leads to directed movement towards external stimuli. The spatio-temporal coordination of these processes depends on the activation of the signaling networks that regulate them at specific subcellular locations. Particularly, the family of small RhoGTPases plays a central role in regulating cell polarization, the formation of adhesion sites and the generation of the forces that drive motion. Theoretical models based on an independent description of these processes have a limited capacity to predict cellular behavior observed in vitro, since their functionality depends on the cross-regulation between their signaling pathways. This thesis presents a model of cell migration that integrates a description of force generation and cell deformation, adhesion site dynamics and RhoGTPases activation. The cell is modeled as a viscoelastic body capable of developing traction and protrusion forces. The forces are determined by the activation level of the RhoGTPases, whose distribution in the cell is described by a set of reaction-diffusion equations. Adhesion sites are modeled as punctual clusters of transmembrane receptors that dynamically bind and unbind the extracellular matrix depending on the force transimtted to them and the distance with ligands coating the substrate. On the theoretical level, the major findings relate the topology of a Crosstalk Scheme and the properties inherited by the associated reaction network as a gradient sensing and regulatory system: reversible polarization, adaptation to uniform stimulus, multi-stimuli response and amplification. Models formulated according to these principles remain functional against the biological diversity associated to different cell types and match the observed behavior in Chemotaxis essays: the capacity of cells to detect shallow gradients, polarize without featuring Turing patterns of activation, and switch the direction of migration after the stimulus source is changed. The biological implications challenge a long held view on the mechanisms of RhoGTPase crosstalk and suggests that the role of GDIs, GEFs and GAPs has to be revised, as supported by recent experimental evidence. In addition, the model recapitulates a continuous transition from the tear-like shape adopted by neutrophiles to the fan-like shape of keratocytes during migration by varying the magnitudes of protrusion and contraction forces or, alternatively, the strength of RhoGTPase Crosstalk. The second mechanism represents a novel explanation of the different morphologies observed in migrating cells. On cell mechanosensing, a new hypothesis is proposed to explain how cells sense the mechanical properties of the ECM. The hypothesis provides a unifying explanation to apparently conflicting observations on force development and growth in real time at cell Focal adhesions, previously attributed to differences in experimental set-ups or cell types studied. An interpretation for the observed relationships between polarization time, migration speed, mechano-sensing limits and substrate rigidity follows from this hypothesis. Further, the theory directly suggests the currently unknown mechanisms that could explain the universal preference of cells (bar neurons) to migrate along stiffness gradients, and for the first time, a plausible biological function for the existence of this phenomenon. It is known as Durotaxis, and its abnormal regulation has been associated to the malignant behaviour of cancer cells.
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Márquez, Rosales Susana Belén. "Modelos físicos de migración en células con morfología no polarizadas." Tesis, Universidad de Chile, 2018. http://repositorio.uchile.cl/handle/2250/168174.

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Magíster en Ciencias, Mención Física
En esta tesis se estudian migraciones celulares en dos sistemas diferentes cuyos agentes comparten la característica de estar no polarizados. Se proponen modelos físicos que en combinación con datos experimentales y simulaciones numéricas buscan reproducir los fenómenos observados con el fin de entenderlos con mayor profundidad y plantear nuevas preguntas de estudio. En la primera parte, el sistema considerado es un pez anual en su etapa de epibolía donde se estudia la migración de las \textit{Deep Cell Layer } (DCL) hacia los bordes de las \textit{Enveloping Cell Layer} (EVL), guiadas por diferencias de dureza. Pese a que al llegar a los bordes las DCL están polarizadas, se desconoce la manera en que a larga distancia las células podrían sensar diferencias mecánicas. Para entender estas observaciones, se plantean tres modelos diferentes que permiten evaluar si los efectos de elasticidad de la EVL y sus bordes (representados por una franja más dura) son percibidos por un agente (DCL) que se encuentre encima generando fuerzas y protrusiones. El primero de ellos considera que las protrusiones generadas por las células se recogen arrugando el sustrato sin deslizar. Los resultados obtenidos demuestran que cuando el sustrato es homogéneo, la célula se comporta como un caminante aleatorio, mientras que en presencia de la franja más dura, el agente se aleja de la misma. El segundo estudio, se hace considerando que las protrusiones al contraerse deslizan y arrugan el sustrato. En este caso en una dimensión, se concluye que el centro de masa de la célula no se desplaza durante la contracción ni para sustratos homogéneos ni bajo la presencia de una franja más dura, lo que permite especular que en dos dimensiones los resultados tampoco mostrarán migración direccionada. Finalmente, se estudia un sustrato sometido a tensiones activas, y, por consiguiente, que considera al tensor de deformaciones no lineal. Para el caso particular de deformaciones lineales se observa un cambio en los coeficientes de difusión cuando el sustrato se contrae lo suficiente. Estos resultados, que permiten hipotetizar acerca del rol de las tensiones internas de los sustratos, que se pueden considerar como un cambio de dureza efectivo \cite{ProfCerdaDurezaEfectiva}, y podría ser más relevante que sus diferencias de dureza, al menos a largas distancias. Por otro lado, se estudia el fenómeno de migración celular colectiva de las \textit{Laterality Organ Progenitors} (LOP) durante la epibolía de los peces cebra. En el proceso, estas células se desplazan asociadas a las \textit{Enveloping Cell Layer} (EVL) desde un polo del huevo al otro. El enlace directo LOP-EVL está presente solo en algunas células y gradualmente se pierde en el proceso. A pesar de eso, y a que las LOPs no se polarizan en ningún momento, logran descender colectivamente y además formar un racimo. Se desarrolla un modelo físico para entender el rol que tiene la adhesión e interacción a larga distancia entre las LOPs. Para simular las protrusiones, se considera que las células se moverán como caminantes aleatorios, y el enlace con las EVL se modela como un resorte. Las dimensiones, condiciones iniciales, coeficientes de difusión, entre otros, se extraen de las observaciones experimentales, mientras que los coeficientes de los potenciales de interacción LOP-LOP se ajustan de modo que las simulaciones reproduzcan las observaciones experimentales de mejor manera. Los resultados obtenidos demuestran que existe un conjunto de parámetros que permiten reproducir tanto la migración colectiva como la formación del racimo, sugiriendo que las protrusiones no direccionadas tienen un rol importante en las migraciones colectivas.
Este trabajo ha sido parcialmente financiado por CONICYT e Iniciativa Científica Milenio
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Jain, Gaurav. "Cell Migration on Opposing Rigidity Protein Gradients: Single Cell and Co-culture Studies." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/70847.

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Cell migration is a complex physiological process that is important from embryogenesis to senescence. In vivo, the migration of cells is guided by a complex combination of signals and cues. Directed migration is typically observed when one of these cues is presented to cells as a gradient. Several studies have been conducted into directed migration on gradients that are purely mechanical or chemical. Our goal was to investigate cellular migratory behavior when cells are presented with a choice and have to choose between increasing substrate rigidity or higher protein concentration. We chose to focus on this unique environment since it recapitulates several interfacial regions in vivo. We have designed novel hydrogels that exhibit dual and opposing chemical and mechanical profiles using photo-polymerization. Our studies demonstrate that durotaxis, a well-known phenomenon, can be reversed when cells sense a steep protein profile in the opposite direction. Fibroblasts were co-cultured with macrophages to obtain an understanding on how migration occurs when two different cell types are present in the same microenvironment. First, we investigated the migratory behavior of macrophages. These cell types exhibited a statistically significant preference to move towards the rigid/low collagen region of the interface. Interestingly, fibroblasts when co-cultured with macrophages, exhibited a preference for the low modulus-high collagen region of the interface. However, with the current sample size, these trends are statistically insignificant. On the contrary, the presence of fibroblasts in the cellular microenvironment did not result in the reversal of durotaxis exhibited by macrophages. Macrophages secreted significantly higher levels of secreted tumor necrosis factor (TNF-alpha) in mono-cultures in contrast to fibroblast-macrophage co-cultures. This trend could be an indication of macrophage plasticity between mono- and co-cultures. In summary, we have designed dual and opposing rigidity-protein gradients on a hydrogel substrate that can provide new insights into cellular locomotion. These results can be used to design biomimetic interfaces, biomaterial implants and for tissue engineering applications.
Ph. D.
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Castro, Nava Arturo Verfasser], Laporte Laura [Akademischer Betreuer] De, and Martin [Akademischer Betreuer] [Möller. "A light-modulated hydrogel system to analyze cell durotaxic behavior in a dynamic manner / Arturo Castro Nava ; Laura De Laporte, Martin Möller." Aachen : Universitätsbibliothek der RWTH Aachen, 2021. http://d-nb.info/1238603114/34.

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Book chapters on the topic "Durotaxie"

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Kidoaki, Satoru. "Chapter 12. Manipulation of Durotaxis on a Matrix with Cell-scale Stiffness Heterogeneity." In Biomaterials Science Series, 265–81. Cambridge: Royal Society of Chemistry, 2022. http://dx.doi.org/10.1039/9781839165375-00265.

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Poh, Chieng Ling. "Computational Studies of Cell Durotaxis on Extracellular Matrix Rigidity Gradients as a Model for Wound Healing and Fibrosis." In IRC-SET 2020, 163–74. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-15-9472-4_14.

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Conference papers on the topic "Durotaxie"

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Sochol, Ryan D., Adrienne T. Higa, Randall R. R. Janairo, Annie Chou, Song Li, and Liwei Lin. "Unidirectional cellular durotaxis via microfabricated posts of varying anisotropy." In TRANSDUCERS 2009 - 2009 International Solid-State Sensors, Actuators and Microsystems Conference. IEEE, 2009. http://dx.doi.org/10.1109/sensor.2009.5285397.

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Zhou, Y., T. Guo, S. Z. Yang, Y. Zhu, C. S. Jiang, and H. Peng. "Mitochondrial Fission and Bioenergetics Mediate Human Lung Fibroblast Durotaxis." In American Thoracic Society 2022 International Conference, May 13-18, 2022 - San Francisco, CA. American Thoracic Society, 2022. http://dx.doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a5224.

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Reinhardt, James W., Daniel A. Krakauer, and Keith J. Gooch. "Complex Matrix Remodeling and Durotaxis Can Emerge From Simple Rules for Cell-Matrix Interaction in Agent-Based Models." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14295.

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Using a top-down approach, an agent-based model was developed within Netlogo where cells and extracellular matrix (ECM) fibers were composed of multiple agents to create deformable structures capable of exerting, reacting to and transmitting mechanical forces. Simulated cells remodeled the fibrous matrix to change both the density and alignment of the fibers and migrated within the matrix in ways that are consistent with previous experimental work. Cells compacted the matrix in their pericellular regions much more than the average compaction experienced for the entire matrix. Between pairs of cells, the anisotropy index increased, fibers became more aligned in the direction parallel to a line connecting the two cells and the matrix density increased. To explore the potential contribution of matrix stiffness gradients in the observed migration (i.e., durotaxis), a single-cell on a regular lattice of fibers possessing a stiffness gradient was simulated. Cells migrated preferentially in the direction of increasing stiffness at a rate of ∼2 cell diameter per 10,000 AU. This work demonstrates that matrix remodeling and durotaxis, both complex phenomena, might be emergent behaviors based on just a few rules that control how a cell can interact with a fibrous ECM.
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Ganzleben, I., M. A. Chrysovergi, T. A. Al-Hilal, F. Liu, A. Santos, L. G. Vincent, C. Happe, et al. "Durotaxis in Lung Fibrosis: Transitioning from In Vitro Mechanisms to In Vivo Imaging." In American Thoracic Society 2022 International Conference, May 13-18, 2022 - San Francisco, CA. American Thoracic Society, 2022. http://dx.doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a5551.

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Chang, Wei-Jen, Nadeen Chahine, and Pen-Hsiu Grace Chao. "Effects of Composite Substrate Microstructure on Fibroblast Morphology and Migration." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53859.

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Many studies have focused on the effects of substrate rigidity on cell traction, migration, and differentiation [1–3]. Most cells are known to migrate toward the stiffer substrate, a phenomenon known as durotaxis. Recent reports have also demonstrated the ‘depth-sensing’ ability of cells on soft hydrogels where cell behaviors on thin gels are more similar to those on stiffer substrates [4–5]. Taking advantage of the high fidelity of microfabrication and soft lithography products, we created novel composite substrates composed of a top layer of collagen hydrogel and an underlying microstructure of silicon elastomer. We hypothesize that cells can sense the underlying microstructures and regulate cell translocation and morphology accordingly.
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Huang, Alvin. "From Bones to Bricks: Design the 3D Printed Durotaxis Chair and La Burbuja Lamp." In ACADIA 2016: Post-Human Frontiers. ACADIA, 2016. http://dx.doi.org/10.52842/conf.acadia.2016.318.

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Huang, Alvin. "From Bones to Bricks: Design the 3D Printed Durotaxis Chair and La Burbuja Lamp." In ACADIA 2016: Post-Human Frontiers. ACADIA, 2016. http://dx.doi.org/10.52842/conf.acadia.2016.318.

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Engler, Adam J. "Probing Mechanisms of Mechano-Sensitive Differentiation in Mesenchymal Stem Cells." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19184.

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Adult mesenchymal stem cells (MSCs) have recently been shown to be responsive to the properties of their adjacent extracellular niche, most notably physical parameters such as topography and elasticity. Elasticity varies dramatically between tissues that MSCs inhibit, which drives elasticity-based differentiation into neurons, muscle, bone, etc. However within tissues, distinct elasticity gradients, brought on by pathological conditions, e.g. myocardial infarction ∼ 8.67 ± 1.50 kPa/mm, or through normal tissue variation, e.g. 0.58 ± 0.88 kPa/mm, could drive MSC migration. In fact, MSCs appear to undergo directed migration up elasticity gradients, or “durotax,” as shallow as 0.96 kPa/mm, indicating a ‘differentiation hierarchy’ since when given the choice, MSCs will durotax into the stiffest regions of the niche and then differentiate based on niche elasticity. As cells move up the gradient, they do so by deforming their niche to determine it’s elasticity, but the molecular mechanism that converts this biophysical signal into a biochemical one which the nucleus can interpret is yet unresolved. We have identified several focal adhesion-related proteins may be capable of force-induced conformational changes, e.g. vinculin. Upon the application of different amounts of traction stress in situ by MSCs, an appropriate amount of stretching results in the exposure of cryptic MAPK binding sites within vinculin and suggests that vinculin, among other focal adhesion proteins, may be sensitive to physical ECM properties and thus able to relay information leading to differentiation of stem cells.
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