scholarly journals Integrin α5β1 nano-presentation regulates collective keratinocyte migration independent of substrate rigidity

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jacopo Di Russo ◽  
Jennifer L Young ◽  
Julian WR Wegner ◽  
Timmy Steins ◽  
Horst Kessler ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Cell Monolayer ◽  
Collective Cell Migration ◽  
Integrin Α5β1 ◽  
Migration Ability ◽  
Fibronectin Receptor ◽  
Substrate Rigidity ◽  
Scale Properties ◽  
Extracellular Matrix Receptors

Nanometer-scale properties of the extracellular matrix influence many biological processes, including cell motility. While much information is available for single-cell migration, to date, no knowledge exists on how the nanoscale presentation of extracellular matrix receptors influences collective cell migration. In wound healing, basal keratinocytes collectively migrate on a fibronectin-rich provisional basement membrane to re-epithelialize the injured skin. Among other receptors, the fibronectin receptor integrin α5β1 plays a pivotal role in this process. Using a highly specific integrin α5β1 peptidomimetic combined with nanopatterned hydrogels, we show that keratinocyte sheets regulate their migration ability at an optimal integrin α5β1 nanospacing. This efficiency relies on the effective propagation of stresses within the cell monolayer independent of substrate stiffness. For the first time, this work highlights the importance of extracellular matrix receptor nanoscale organization required for efficient tissue regeneration.

scholarly journals Integrin α5β1 nano-presentation regulates collective keratinocyte migration independent of substrate rigidity

2021 ◽  
Author(s):  
Jacopo Di Russo ◽  
Jennifer L. Young ◽  
Julian W. R. Wegner ◽  
Timmy Steins ◽  
Horst Kessler ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Cell Monolayer ◽  
Collective Cell Migration ◽  
Integrin Α5β1 ◽  
Migration Ability ◽  
Fibronectin Receptor ◽  
Substrate Rigidity ◽  
Scale Properties ◽  
Extracellular Matrix Receptors

AbstractNanometer-scale properties of the extracellular matrix influence many biological processes, including cell motility. While much information is available for single cell migration, to date, no knowledge exists on how the nanoscale presentation of extracellular matrix receptors influences collective cell migration. In wound healing, basal keratinocytes collectively migrate on a fibronectin-rich provisional basement membrane to re-epithelialize the injured skin. Among other receptors, the fibronectin receptor integrin α5β1 plays a pivotal role in this process. Using a highly specific integrin α5β1 peptidomimetic combined with nanopatterned hydrogels, we show that keratinocyte sheets regulate their migration ability at an optimal integrin α5β1 nanospacing. This efficiency relies on the effective propagation of stresses within the cell monolayer independent of substrate stiffness. For the first time, this work highlights the importance of extracellular matrix receptor nanoscale organization required for efficient tissue regeneration.

scholarly journals Collective cell migration without proliferation: density determines cell velocity and wave velocity

2018 ◽  
Vol 5 (5) ◽  
pp. 172421 ◽  
Author(s):  
Sham Tlili ◽  
Estelle Gauquelin ◽  
Brigitte Li ◽  
Olivier Cardoso ◽  
Benoît Ladoux ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Density ◽  
Wave Velocity ◽  
Cell Monolayer ◽  
Leading Edge ◽  
Collective Cell Migration ◽  
Tumour Metastasis ◽  
Long Duration ◽  
Cell Velocity ◽  
Moving Front

Collective cell migration contributes to embryogenesis, wound healing and tumour metastasis. Cell monolayer migration experiments help in understanding what determines the movement of cells far from the leading edge. Inhibiting cell proliferation limits cell density increase and prevents jamming; we observe long-duration migration and quantify space–time characteristics of the velocity profile over large length scales and time scales. Velocity waves propagate backwards and their frequency depends only on cell density at the moving front. Both cell average velocity and wave velocity increase linearly with the cell effective radius regardless of the distance to the front. Inhibiting lamellipodia decreases cell velocity while waves either disappear or have a lower frequency. Our model combines conservation laws, monolayer mechanical properties and a phenomenological coupling between strain and polarity: advancing cells pull on their followers, which then become polarized. With reasonable values of parameters, this model agrees with several of our experimental observations. Together, our experiments and model disantangle the respective contributions of active velocity and of proliferation in monolayer migration, explain how cells maintain their polarity far from the moving front, and highlight the importance of strain–polarity coupling and density in long-range information propagation.

scholarly journals A Key Regulator of Cell Adhesion: Identification and Characterization of Important N-Glycosylation Sites on Integrin α5 for Cell Migration

2017 ◽  
Vol 37 (9) ◽  
Author(s):  
Qinglei Hang ◽  
Tomoya Isaji ◽  
Sicong Hou ◽  
Yuqin Wang ◽  
Tomohiko Fukuda ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Fiber Formation ◽  
Actin Stress Fiber ◽  
Loss Of Function ◽  
Integrin Α5β1 ◽  
Migration Ability ◽  
Cell Adhesion And Migration ◽  
Integrin Α5

ABSTRACT The N-glycosylation of integrin α5β1 is thought to control many fundamental aspects of cell behavior, including cell adhesion and migration. However, the mechanism of how N-glycans function remains largely obscure. Here, we used a loss-of-function approach. Wild-type (WT) integrin α5 and N-glycosylation mutant S3-5 (sites 3 to 5) integrin α5, which contains fewer N-glycans, were stably reconstituted in α5 knockout cancer cells. We found that the migration ability of S3-5 cells was decreased in comparison with that of the WT. Interestingly, the levels of phosphorylated focal adhesion kinase and actin stress fiber formation were greatly enhanced in the S3-5 mutant. In a mechanistic manner, the internalization of active but not total integrin α5β1 was inhibited in S3-5 cells, which is a process that is related to the enhanced expression of active integrin α5β1 on the cell surface. Importantly, restoration of N-glycosylation on the β-propeller domain of α5 reinstated the cell migration ability, active α5β1 expression, and internalization. Moreover, these N-glycans are critical for α5–syndecan-4 complex formation. These findings indicate that N-glycosylation on the β-propeller domain functions as a molecular switch to control the dynamics of α5β1 on the cell surface that in turn is required for optimum adhesion for cell migration.

scholarly journals Zyxin Is Involved in Fibroblast Rigidity Sensing and Durotaxis

2021 ◽  
Vol 9 ◽  
Author(s):  
Ai Kia Yip ◽  
Songjing Zhang ◽  
Lor Huai Chong ◽  
Elsie Cheruba ◽  
Jessie Yong Xing Woon ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Focal Adhesions ◽  
Wild Type ◽  
Actin Organization ◽  
Rigidity Sensing ◽  
Substrate Rigidity ◽  
Cell Traction ◽  
Traction Stress

Focal adhesions (FAs) are specialized structures that enable cells to sense their extracellular matrix rigidity and transmit these signals to the interior of the cells, bringing about actin cytoskeleton reorganization, FA maturation, and cell migration. It is known that cells migrate towards regions of higher substrate rigidity, a phenomenon known as durotaxis. However, the underlying molecular mechanism of durotaxis and how different proteins in the FA are involved remain unclear. Zyxin is a component of the FA that has been implicated in connecting the actin cytoskeleton to the FA. We have found that knocking down zyxin impaired NIH3T3 fibroblast’s ability to sense and respond to changes in extracellular matrix in terms of their FA sizes, cell traction stress magnitudes and F-actin organization. Cell migration speed of zyxin knockdown fibroblasts was also independent of the underlying substrate rigidity, unlike wild type fibroblasts which migrated fastest at an intermediate substrate rigidity of 14 kPa. Wild type fibroblasts exhibited durotaxis by migrating toward regions of increasing substrate rigidity on polyacrylamide gels with substrate rigidity gradient, while zyxin knockdown fibroblasts did not exhibit durotaxis. Therefore, we propose zyxin as an essential protein that is required for rigidity sensing and durotaxis through modulating FA sizes, cell traction stress and F-actin organization.

scholarly journals Collective cell migration without proliferation: density determines cell velocity and wave velocity

2017 ◽  
Author(s):  
Sham Tlili ◽  
Estelle Gauquelin ◽  
Brigitte Li ◽  
Olivier Cardoso ◽  
Benoît Ladoux ◽  
...  
Keyword(s):  
Cell Migration ◽  
Wave Velocity ◽  
Signal To Noise Ratio ◽  
Cell Monolayer ◽  
Temporal Analysis ◽  
Collective Cell Migration ◽  
Cell Radius ◽  
Cell Velocity ◽  
Spatio Temporal ◽  
Parameter Values

AbstractCollective cell migration contributes to morphogenesis, wound healing or tumor metastasis. Culturing epithelial monolayers on a substrate enables to quantify such tissue migration. By using narrow strips, we stabilise the front shape; by inhibiting cell division, we limit density increase and favor steady migration; by using long strips, we observe a confined cell monolayer migrating over days. A coherent collective movement propagates over millimeters; cells spread and density decreases from the monolayer bulk toward the front. Cell velocity (∼micrometer per minute) increases linearly with cell radius, and does not depend explicitly on the distance to the front. Over ten periods of backwards propagating velocity waves, with wavelength ∼millimeter, are detected with a signal-to-noise ratio enabling for quantitative spatio-temporal analysis. Their velocity (∼ten micrometers per minute) is ten times the cell velocity; it increases linearly with the cell radius. Their period (∼two hours) is spatially homogeneous, and increases with the front density. When we inhibit the formation of lamellipodia, cell velocity drops while waves either disappear, or have a smaller amplitude and slower period. Our phenomenological model assumes that both cell and wave velocities are related with the activity of lamellipodia, and that the local stretching in the monolayer bulk modulates traction stresses. We find that parameter values close to the instability limit where waves appear yield qualitative and quantitative predictions compatible with experiments, including the facts that: waves propagate backwards; wave velocity increases with cell radius; lamellipodia inhibition attenuates, slows down or even suppresses the waves. Together, our experiments and modelling evidence the importance of lamellipodia in collective cell migration and waves.

scholarly journals A Photoactivatable Nanopatterned Substrate for Analyzing Collective Cell Migration with Precisely Tuned Cell-Extracellular Matrix Ligand Interactions

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e91875 ◽  
Author(s):  
Yoshihisa Shimizu ◽  
Heike Boehm ◽  
Kazuo Yamaguchi ◽  
Joachim P. Spatz ◽  
Jun Nakanishi
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Collective Cell Migration ◽  
Ligand Interactions

scholarly journals Binding of ZO-1 to α5β1 integrins regulates the mechanical properties of α5β1–fibronectin links

2017 ◽  
Vol 28 (14) ◽  
pp. 1847-1852 ◽  
Author(s):  
Víctor González-Tarragó ◽  
Alberto Elosegui-Artola ◽  
Elsa Bazellières ◽  
Roger Oria ◽  
Carlos Pérez-González ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Integrin Α5β1 ◽  
Cell Monolayers ◽  
And Migration ◽  
Integrin Regulation ◽  
In Cells

Fundamental processes in cell adhesion, motility, and rigidity adaptation are regulated by integrin-mediated adhesion to the extracellular matrix (ECM). The link between the ECM component fibronectin (fn) and integrin α5β1 forms a complex with ZO-1 in cells at the edge of migrating monolayers, regulating cell migration. However, how this complex affects the α5β1-fn link is unknown. Here we show that the α5β1/ZO-1 complex decreases the resistance to force of α5β1–fn adhesions located at the edge of migrating cell monolayers while also increasing α5β1 recruitment. Consistently with a molecular clutch model of adhesion, this effect of ZO-1 leads to a decrease in the density and intensity of adhesions in cells at the edge of migrating monolayers. Taken together, our results unveil a new mode of integrin regulation through modification of the mechanical properties of integrin–ECM links, which may be harnessed by cells to control adhesion and migration.

scholarly journals One-dimensional collective migration of a proliferating cell monolayer

Soft Matter ◽  
2016 ◽  
Vol 12 (8) ◽  
pp. 2381-2391 ◽  
Author(s):  
Pierre Recho ◽  
Jonas Ranft ◽  
Philippe Marcq
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Monolayer ◽  
Spatial Dimension ◽  
Front Velocity ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Cell Sheets ◽  
One Dimensional ◽  
Proliferating Cell

Motivated by recent experiments on the expansion of highly cohesive cell sheets, our model of collective cell migration in one spatial dimension shows that constant front velocity results from the combined mechanical effects of bulk cell proliferation and front lamellipodial activity.

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