Mechanotransduction of substrate stiffness in endothelial cell collective migration

2021 ◽  
Author(s):  
Adam Charles Canver
Keyword(s):  
Endothelial Cell ◽  
Substrate Stiffness ◽  
Collective Migration ◽  
Cell Collective

scholarly journals PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jesús Gómez-Escudero ◽  
Cristina Clemente ◽  
Diego García-Weber ◽  
Rebeca Acín-Pérez ◽  
Jaime Millán ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Inflammatory Disease ◽  
Chronic Inflammatory Disease ◽  
Cell Junctions ◽  
Cell Junction ◽  
Collective Migration ◽  
Sprouting Angiogenesis ◽  
Cell Cell

Abstract Angiogenesis, the formation of new blood vessels from pre-existing ones, occurs in pathophysiological contexts such as wound healing, cancer, and chronic inflammatory disease. During sprouting angiogenesis, endothelial tip and stalk cells coordinately remodel their cell-cell junctions to allow collective migration and extension of the sprout while maintaining barrier integrity. All these processes require energy, and the predominant ATP generation route in endothelial cells is glycolysis. However, it remains unclear how ATP reaches the plasma membrane and intercellular junctions. In this study, we demonstrate that the glycolytic enzyme pyruvate kinase 2 (PKM2) is required for sprouting angiogenesis in vitro and in vivo through the regulation of endothelial cell-junction dynamics and collective migration. We show that PKM2-silencing decreases ATP required for proper VE-cadherin internalization/traffic at endothelial cell-cell junctions. Our study provides fresh insight into the role of ATP subcellular compartmentalization in endothelial cells during angiogenesis. Since manipulation of EC glycolysis constitutes a potential therapeutic intervention route, particularly in tumors and chronic inflammatory disease, these findings may help to refine the targeting of endothelial glycolytic activity in disease.

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 ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Substrate Stiffness ◽  
Collective Migration ◽  
Cell Clusters ◽  
Physical Cues ◽  
Extracellular Environment

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

scholarly journals Impact of Na+ permeation on collective migration of pulmonary arterial endothelial cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250095
Author(s):  
Ningyong Xu ◽  
Linn Ayers ◽  
Viktoriya Pastukh ◽  
Mikhail Alexeyev ◽  
Troy Stevens ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Wound Closure ◽  
Combined Treatment ◽  
Intercellular Adhesion ◽  
Second Phase ◽  
Collective Migration ◽  
Channel Protein ◽  
Pharmacological Inhibition ◽  
Floating Particles

Collective migration of endothelial cells is important for wound healing and angiogenesis. During such migration, each constituent endothelial cell coordinates its magnitude and direction of migration with its neighbors while retaining intercellular adhesion. Ensuring coordination and cohesion involves a variety of intra- and inter-cellular signaling processes. However, the role of permeation of extracellular Na+ in collective cell migration remains unclear. Here, we examined the effect of Na+ permeation in collective migration of pulmonary artery endothelial cell (PAEC) monolayers triggered by either a scratch injury or a barrier removal over 24 hours. In the scratch assay, PAEC monolayers migrated in two approximately linear phases. In the first phase, wound closure started with fast speed which then rapidly reduced within 5 hours after scratching. In the second phase, wound closure maintained at slow and stable speed from 6 to 24 hours. In the absence of extracellular Na+, the wound closure distance was reduced by >50%. Fewer cells at the leading edge protruded prominent lamellipodia. Beside transient gaps, some sustained interendothelial gaps also formed and progressively increased in size over time, and some fused with adjacent gaps. In the absence of both Na+ and scratch injury, PAEC monolayer migrated even more slowly, and interendothelial gaps obviously increased in size towards the end. Pharmacological inhibition of the epithelial Na+ channel (ENaC) using amiloride reduced wound closure distance by 30%. Inhibition of both the ENaC and the Na+/Ca2+ exchanger (NCX) using benzamil further reduced wound closure distance in the second phase and caused accumulation of floating particles in the media. Surprisingly, pharmacological inhibition of the Ca2+ release-activated Ca2+ (CRAC) channel protein 1 (Orai1) using GSK-7975A, the transient receptor potential channel protein 1 and 4 (TRPC1/4) using Pico145, or both Orai1 and TRPC1/4 using combined GSK-7975A and Pico145 treatment did not affect wound closure distance dramatically. Nevertheless, the combined treatment appeared to cause accumulation of floating particles. Note that GSK-7975A also inhibits small inward Ca2+ currents via Orai2 and Orai3 channels, whereas Pico145 also blocks TRPC4, TRPC5, and TRPC1/5 channels. By contrast, gene silence of Orai1 by shRNAs led to a 25% reduction of wound closure in the first 6 hours but had no effect afterwards. However, in the absence of extracellular Na+ or cellular injury, Orai1 did not affect PAEC collective migration. Overall, the data reveal that Na+ permeation into cells contributes to PAEC monolayer collective migration by increasing lamellipodial formation, reducing accumulation of floating particles, and improving intercellular adhesion.

scholarly journals Topography-induced large-scale anti-parallel collective migration in vascular endothelium

2021 ◽  
Author(s):  
Claire Leclech ◽  
David Gonzalez-Rodriguez ◽  
Aur&eacutelien Villedieu ◽  
Th&eacutevy Lok ◽  
Anne-Marie D&eacuteplanche ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cell ◽  
Intact Cell ◽  
Cell Sheet ◽  
Cell Junctions ◽  
Periodic Pattern ◽  
Physical Factors ◽  
Collective Migration ◽  
Cell Assemblies ◽  
Collective Movement

Collective migration of vascular endothelial cells is central for embryonic development, angiogenesis, and wound closure. Although physical confinement of cell assemblies has been shown to elicit specific patterns of collective movement in various cell types, endothelial migration in vivo often occurs without confinement. Here we show that unconfined endothelial cell monolayers on microgrooved substrates that mimic the anisotropic organization of the extracellular matrix exhibit a new type of collective movement that takes the form of a periodic pattern of anti-parallel cell streams. We further establish that the development of these streams requires intact cell-cell junctions and that stream sizes are particularly sensitive to groove depth. Finally, we show that modeling the endothelial cell sheet as an active fluid with the microgrooves acting as constraints on cell orientation predicts the occurrence of the periodic anti-parallel cell streams as well as their lengths and widths. We posit that in unconfined cell assemblies, physical factors that constrain or bias cellular orientation such as anisotropic extracellular matrix cues or directed flow-derived shear forces dictate the pattern of collective cell movement.

Substrate stiffness modulates endothelial cell function via the YAP-Dll4-Notch1 pathway

2021 ◽  
pp. 112835
Author(s):  
Eri Matsuo ◽  
Takayuki Okamoto ◽  
Atsushi Ito ◽  
Eiji Kawamoto ◽  
Kunihiro Asanuma ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Substrate Stiffness ◽  
Endothelial Cell Function

scholarly journals Gold Nanorod Photothermal Therapy Alters Cell Junctions and Actin Network in Inhibiting Cancer Cell Collective Migration

ACS Nano ◽  
2018 ◽  
Vol 12 (9) ◽  
pp. 9279-9290 ◽  
Author(s):  
Yue Wu ◽  
Moustafa R. K. Ali ◽  
Bin Dong ◽  
Tiegang Han ◽  
Kuangcai Chen ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Photothermal Therapy ◽  
Gold Nanorod ◽  
Cell Junctions ◽  
Actin Network ◽  
Collective Migration ◽  
Cell Collective

scholarly journals Extracellular matrix stiffness modulates VEGF calcium signaling in endothelial cells: individual cell and population analysis

2015 ◽  
Vol 7 (9) ◽  
pp. 1011-1025 ◽  
Author(s):  
Kelsey E. Derricks ◽  
Vickery Trinkaus-Randall ◽  
Matthew A. Nugent
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Individual Cell ◽  
Population Analysis ◽  
Substrate Stiffness ◽  
Matrix Stiffness ◽  
Cell Responses ◽  
Signaling Dynamics ◽  
Extracellular Matrix Stiffness

Endothelial cell responses to VEGF are heterogeneous and vary with ECM stiffness. We analyzed individual cell responses to VEGF as a function of substrate stiffness to identify unique clusters of cell signaling dynamics.

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