scholarly journals A subtle relationship between substrate stiffness and collective migration of cell clusters

Soft Matter ◽  
2020 ◽  
Vol 16 (7) ◽  
pp. 1825-1839 ◽  
Author(s):  
Hayri E. Balcioglu ◽  
Lakshmi Balasubramaniam ◽  
Tomita Vasilica Stirbat ◽  
Bryant L. Doss ◽  
Marc-Antoine Fardin ◽  
...  

The physical cues from the extracellular environment mediates cell signaling spatially and temporally.

Author(s):  
Kelly C. Clause ◽  
Tatiana Segura ◽  
Thomas H. Barker

Growing evidence suggests that physical microenvironments and mechanical stresses direct cell fate in developing tissues. However, how these physical properties affect morphogenesis remains unknown. We show here that ECM mechanical properties, i.e. stiffness, reproduced by using hydrogel, guide tissue morphogenesis in the developing lung bud. In particular, decreasing substrate stiffness in cultured lung buds resulted in an inhibition of appropriate cleft formation and a resulting enlargement of epithelial buds. These findings suggest that the magnitude of mechanical stiffness across the lung bud alters the branching pattern. Additionally, physically designed hydrogel material is a valuable tool for producing the specific microenvironment to explore how physical cues affect and alter tissue morphogenesis for in vitro study.


2020 ◽  
Vol 19 (5) ◽  
pp. 1551-1564 ◽  
Author(s):  
Tyler A. Collins ◽  
Benjamin M. Yeoman ◽  
Parag Katira

2018 ◽  
Vol 444 ◽  
pp. S262-S273 ◽  
Author(s):  
Brian Merchant ◽  
Leah Edelstein-Keshet ◽  
James J. Feng

1998 ◽  
Vol 78 (3) ◽  
pp. 763-781 ◽  
Author(s):  
PAUL A. JANMEY

Janmey, Paul A. The Cytoskeleton and Cell Signaling: Component Localization and Mechanical Coupling. Physiol. Rev. 78: 763–781, 1998. — The three-dimensional intracellular network formed by the filamentous polymers comprising the cytoskeletal affects the way cells sense their extracellular environment and respond to stimuli. Because the cytoskeleton is viscoelastic, it provides a continuous mechanical coupling throughout the cell that changes as the cytoskeleton remodels. Such mechanical effects, based on network formation, can influence ion channel activity at the plasma membrane of cells and may conduct mechanical stresses from the cell membrane to internal organelles. As a result, both rapid responses such as changes in intracellular Ca2+ and slower responses such as gene transcription or the onset of apoptosis can be elicited or modulated by mechanical perturbations. In addition to mechanical features, the cytoskeleton also provides a large negatively charged surface on which many signaling molecules including protein and lipid kinases, phospholipases, and GTPases localize in response to activation of specific transmembrane receptors. The resulting spatial localization and concomitant change in enzymatic activity can alter the magnitude and limit the range of intracellular signaling events.


2017 ◽  
Author(s):  
Brian Merchant ◽  
Leah Edelstein-Keshet ◽  
James J. Feng

AbstractWe propose a model to explain the spontaneous collective migration of neural crest cells in the absence of an external gradient of chemoattractants. The model is based on the dynamical interaction between Rac1 and RhoA that is known to regulate the polarization, contact inhibition and co-attraction of neural crest cells. Coupling the reaction-diffusion equations for active and inactive Rac1 and RhoA on the cell membrane with a mechanical model for the overdamped motion of membrane vertices, we show that co-attraction and contact inhibition cooperate to produce persistence of polarity in a cluster of neural crest cells by suppressing the random onset of Rac1 hotspots that may mature into new protrusion fronts. This produces persistent directional migration of cell clusters in corridors. Our model confirms a prior hypothesis that co-attraction and contact inhibition are key to spontaneous collective migration, and provides an explanation of their cooperative working mechanism in terms of Rho GTPase signaling. The model shows that the spontaneous migration is more robust for larger clusters, and is most efficient in a corridor of optimal confinement.


2020 ◽  
Author(s):  
Diane-Laure Pagès ◽  
Emmanuel Dornier ◽  
Jean De Seze ◽  
Li Wang ◽  
Rui Luan ◽  
...  

AbstractCell migration is essential to most living organisms. Single cell migration involves two distinct mechanisms, either a focal adhesion- and traction-dependent mesenchymal motility or an adhesion-independent but contractility-driven propulsive amoeboid locomotion. Cohesive migration of a group of cells, also called collective cell migration, has been only described as an adhesion- and traction-dependent mode of locomotion where the driving forces are mostly exerted at the front by leader cells. Here, by studying primary cancer specimens and cell lines from colorectal cancer, we demonstrate the existence of a second mode of collective migration which does not require adhesion to the surroundings and relies on a polarised supracellular contractility. Cell clusters confined into non-adhesive microchannels migrate in a rounded morphology, independently of the formation of focal adhesions or protruding leader cells, and lacking internal flow of cells, ruling-out classical traction-driven collective migration. Like single cells migrating in an amoeboid fashion, the clusters display a supracellular actin cortex with myosin II enriched at the rear. Using pharmacological inhibitors and optogenetics, we show that this polarised actomyosin activity powers migration and propels the clusters. This new mode of migration, that we named collective amoeboid, could be enabled by intrinsic or extrinsic neoplasic features to enable the metastatic spread of cancers.One Sentence SummaryClusters organise as polarised and contractile super-cells to migrate without adhesion.


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