scholarly journals Heterogenous adhesion of follower cells affects tension profile and velocity of leader cells in primary keratocyte collective cell migration

2020 ◽  
Author(s):  
Baishali Mukherjee ◽  
Madhura Chakraborty ◽  
Arikta Biswas ◽  
Rajesh Kumble Nayak ◽  
Bidisha Sinha
Keyword(s):  
Cell Migration ◽  
Single Cell ◽  
Cell Interactions ◽  
Collective Cell Migration ◽  
Membrane Tension ◽  
High Cell ◽  
Cell Sheets ◽  
Membrane Fluctuations ◽  
High Tension ◽  
Cell To Cell Variability

AbstractSingle cell studies demonstrate membrane tension to be a central regulator of lamellipodia-driven motility bringing in front-coherence. During collective cell migration, however, tension mapping or existence of intracellular tension-gradients and the effect of cell-cell interactions have remained unexplored. In this study of membrane fluctuations and fluctuation-tension of migrating primary keratocyte cell-sheets, we first show that some leader cells are followed by followers which remain de-adhered from the substrate while being attached to other cells and thus appear to be “taking a ride”. A subtle yet significant enhanced long-timescale velocity in these leaders indicate increased directionality. Intriguingly, such leaders mostly have front-high tension gradients like single keratocytes, while followers and other leaders usually display front-low membrane tension gradients. The front-high tension gradient and higher membrane tension observed in these leaders, despite the high cell-to-cell variability in membrane tension demonstrate how leader-follower interactions and heterogenous adhesion profiles are key in collective cell migration.

scholarly journals NudCL2 regulates cell migration by stabilizing both myosin-9 and LIS1 with Hsp90

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Wenwen Chen ◽  
Wei Wang ◽  
Xiaoxia Sun ◽  
Shanshan Xie ◽  
Xiaoyang Xu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Single Cell ◽  
Mammalian Cells ◽  
Ectopic Expression ◽  
Heat Shock Protein 90 ◽  
Underlying Mechanism ◽  
Collective Cell Migration ◽  
Interacting Protein ◽  
Protein Levels ◽  
Protein Instability

Abstract Cell migration plays pivotal roles in many biological processes; however, its underlying mechanism remains unclear. Here, we find that NudC-like protein 2 (NudCL2), a cochaperone of heat shock protein 90 (Hsp90), modulates cell migration by stabilizing both myosin-9 and lissencephaly protein 1 (LIS1). Either knockdown or knockout of NudCL2 significantly increases single-cell migration, but has no significant effect on collective cell migration. Immunoprecipitation–mass spectrometry and western blotting analyses reveal that NudCL2 binds to myosin-9 in mammalian cells. Depletion of NudCL2 not only decreases myosin-9 protein levels, but also results in actin disorganization. Ectopic expression of myosin-9 efficiently reverses defects in actin disorganization and single-cell migration in cells depleted of NudCL2. Interestingly, knockdown of myosin-9 increases both single and collective cell migration. Depletion of LIS1, a NudCL2 client protein, suppresses both single and collective cell migration, which exhibits the opposite effect compared with myosin-9 depletion. Co-depletion of myosin-9 and LIS1 promotes single-cell migration, resembling the phenotype caused by NudCL2 depletion. Furthermore, inhibition of Hsp90 ATPase activity also reduces the Hsp90-interacting protein myosin-9 stability and increases single-cell migration. Forced expression of Hsp90 efficiently reverses myosin-9 protein instability and the defects induced by NudCL2 depletion, but not vice versa. Taken together, these data suggest that NudCL2 plays an important role in the precise regulation of cell migration by stabilizing both myosin-9 and LIS1 via Hsp90 pathway.

scholarly journals Cell interactions in collective cell migration

Development ◽  
2019 ◽  
Vol 146 (23) ◽  
pp. dev172056 ◽  
Author(s):  
Abhinava K. Mishra ◽  
Joseph P. Campanale ◽  
James A. Mondo ◽  
Denise J. Montell
Keyword(s):  
Cell Migration ◽  
Cell Interactions ◽  
Collective Cell Migration

scholarly journals HAX1 impact on collective cell migration, cell adhesion, and cell shape is linked to the regulation of actomyosin contractility

2019 ◽  
Vol 30 (25) ◽  
pp. 3024-3036 ◽  
Author(s):  
Anna Balcerak ◽  
Alicja Trebinska-Stryjewska ◽  
Maciej Wakula ◽  
Mateusz Chmielarczyk ◽  
Urszula Smietanka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Single Cell ◽  
Cancer Progression ◽  
Cancer Cell Line ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Actomyosin Contractility ◽  
Epithelial Cell Layer ◽  
Cell Cell

HAX1 protein is involved in the regulation of apoptosis, cell motility and calcium homeostasis. Its overexpression was reported in several tumors, including breast cancer. This study demonstrates that HAX1 has an impact on collective, but not single-cell migration, thus indicating the importance of cell–cell contacts for the HAX1-mediated effect. Accordingly, it was shown that HAX1 knockdown affects cell–cell junctions, substrate adhesion, and epithelial cell layer integrity. As demonstrated here, these effects can be attributed to the modulation of actomyosin contractility through changes in RhoA and septin signaling. Additionally, it was shown that HAX1 does not influence invasive potential in the breast cancer cell line, suggesting that its role in breast cancer progression may be linked instead to collective invasion of the epithelial cells but not single-cell dissemination.

scholarly journals Directional Collective Cell Migration Emerges as a Property of Cell Interactions

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e104969 ◽  
Author(s):  
Mae L. Woods ◽  
Carlos Carmona-Fontaine ◽  
Chris P. Barnes ◽  
Iain D. Couzin ◽  
Roberto Mayor ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Interactions ◽  
Collective Cell Migration

scholarly journals Aligned fibers direct collective cell migration to engineer closing and nonclosing wound gaps

2017 ◽  
Vol 28 (19) ◽  
pp. 2579-2588 ◽  
Author(s):  
Puja Sharma ◽  
Colin Ng ◽  
Aniket Jana ◽  
Abinash Padhi ◽  
Paige Szymanski ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Biology ◽  
Cancer Metastasis ◽  
Rubber Band ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Cell Sheets ◽  
Cell Monolayers ◽  
Fiber Arrays

Cell emergence onto damaged or organized fibrous extracellular matrix (ECM) is a crucial precursor to collective cell migration in wound closure and cancer metastasis, respectively. However, there is a fundamental gap in our quantitative understanding of the role of local ECM size and arrangement in cell emergence–based migration and local gap closure. Here, using ECM-mimicking nanofibers bridging cell monolayers, we describe a method to recapitulate and quantitatively describe these in vivo behaviors over multispatial (single cell to cell sheets) and temporal (minutes to weeks) scales. On fiber arrays with large interfiber spacing, cells emerge (invade) either singularly by breaking cell–cell junctions analogous to release of a stretched rubber band (recoil), or in groups of few cells (chains), whereas on closely spaced fibers, multiple chains emerge collectively. Advancing cells on fibers form cell streams, which support suspended cell sheets (SCS) of various sizes and curvatures. SCS converge to form local gaps that close based on both the gap size and shape. We document that cell stream spacing of 375 µm and larger hinders SCS advancement, thus providing abilities to engineer closing and nonclosing gaps. Altogether we highlight the importance of studying cell-fiber interactions and matrix structural remodeling in fundamental and translational cell biology.

scholarly journals Single cell gene expression analysis in injury-induced collective cell migration

2014 ◽  
Vol 6 (2) ◽  
pp. 192-202 ◽  
Author(s):  
Reza Riahi ◽  
Min Long ◽  
Yongliang Yang ◽  
Zachary Dean ◽  
Donna D. Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Migration ◽  
Single Cell ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Collective Cell Migration ◽  
Cell Gene Expression ◽  
Cell Gene

scholarly journals Protein phosphatase 1 activity controls a balance between collective and single cell modes of migration

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yujun Chen ◽  
Nirupama Kotian ◽  
George Aranjuez ◽  
Lin Chen ◽  
C Luke Messer ◽  
...  
Keyword(s):  
Cell Migration ◽  
Single Cell ◽  
Protein Phosphatase ◽  
Single Cells ◽  
Cell Junctions ◽  
Protein Phosphatase 1 ◽  
Collective Cell Migration ◽  
Border Cells ◽  
Border Cell ◽  
And Migration

Collective cell migration is central to many developmental and pathological processes. However, the mechanisms that keep cell collectives together and coordinate movement of multiple cells are poorly understood. Using the Drosophila border cell migration model, we find that Protein phosphatase 1 (Pp1) activity controls collective cell cohesion and migration. Inhibition of Pp1 causes border cells to round up, dissociate, and move as single cells with altered motility. We present evidence that Pp1 promotes proper levels of cadherin-catenin complex proteins at cell-cell junctions within the cluster to keep border cells together. Pp1 further restricts actomyosin contractility to the cluster periphery rather than at individual internal border cell contacts. We show that the myosin phosphatase Pp1 complex, which inhibits non-muscle myosin-II (Myo-II) activity, coordinates border cell shape and cluster cohesion. Given the high conservation of Pp1 complexes, this study identifies Pp1 as a major regulator of collective versus single cell migration.

scholarly journals Protein Phosphatase 1 activity controls a balance between collective and single cell modes of migration

2019 ◽  
Author(s):  
Yujun Chen ◽  
Nirupama Kotian ◽  
George Aranjuez ◽  
Lin Chen ◽  
C. Luke Messer ◽  
...  
Keyword(s):  
Cell Migration ◽  
Single Cell ◽  
Protein Phosphatase ◽  
Single Cells ◽  
Cell Junctions ◽  
Protein Phosphatase 1 ◽  
Collective Cell Migration ◽  
Border Cells ◽  
Border Cell ◽  
Cell Cell

AbstractCollective cell migration is central to many developmental and pathological processes. However, the mechanisms that keep cell collectives together and coordinate movement of multiple cells are poorly understood. Using the Drosophila border cell migration model, we find that Protein phosphatase 1 (Pp1) activity controls collective cell cohesion and migration. Inhibition of Pp1 causes border cells to round up, dissociate, and move as single cells with altered motility. We present evidence that Pp1 promotes proper levels of cadherin-catenin complex proteins at cell-cell junctions within the cluster to keep border cells together. Pp1 further restricts actomyosin contractility to the cluster periphery rather than at internal cell-cell contacts. We show that the myosin phosphatase Pp1 complex, which inhibits non-muscle myosin-II (Myo-II) activity, coordinates border cell shape and cluster cohesion. Given the high conservation of Pp1 complexes, this study identifies Pp1 as a major regulator of collective versus single cell migration.

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