Photoactivatable substrates for systematic study of the impact of an extracellular matrix ligand on appearance of leader cells in collective cell migration

Biomaterials ◽  
2018 ◽  
Vol 169 ◽  
pp. 72-84 ◽  
Author(s):  
Shimaa A. Abdellatef ◽  
Jun Nakanishi
2021 ◽  
Author(s):  
Ivana Pajic-Lijakovic ◽  
Milan Milivojevic

Although collective cell migration (CCM) is a highly coordinated migratory mode, perturbations in the form of jamming state transitions and vice versa often occur even in 2D. These perturbations are involved in various biological processes, such as embryogenesis, wound healing and cancer invasion. CCM induces accumulation of cell residual stress which has a feedback impact to cell packing density. Density-mediated change of cell mobility influences the state of viscoelasticity of multicellular systems and on that base the jamming state transition. Although a good comprehension of how cells collectively migrate by following molecular rules has been generated, the impact of cellular rearrangements on cell viscoelasticity remains less understood. Thus, considering the density driven evolution of viscoelasticity caused by reduction of cell mobility could result in a powerful tool in order to address the contribution of cell jamming state transition in CCM and help to understand this important but still controversial topic. In addition, five viscoelastic states gained within three regimes: (1) convective regime, (2) conductive regime, and (3) damped-conductive regime was discussed based on the modeling consideration with special emphasis of jamming and unjamming states.


2021 ◽  
Author(s):  
Jacopo Di Russo ◽  
Jennifer L. Young ◽  
Julian W. R. Wegner ◽  
Timmy Steins ◽  
Horst Kessler ◽  
...  

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.


Author(s):  
Szabolcs Suveges ◽  
Ibrahim Chamseddine ◽  
Katarzyna A. Rejniak ◽  
Raluca Eftimie ◽  
Dumitru Trucu

The specific structure of the extracellular matrix (ECM), and in particular the density and orientation of collagen fibres, plays an important role in the evolution of solid cancers. While many experimental studies discussed the role of ECM in individual and collective cell migration, there are still unanswered questions about the impact of nonlocal cell sensing of other cells on the overall shape of tumour aggregation and its migration type. There are also unanswered questions about the migration and spread of tumour that arises at the boundary between different tissues with different collagen fibre orientations. To address these questions, in this study we develop a hybrid multi-scale model that considers the cells as individual entities and ECM as a continuous field. The numerical simulations obtained through this model match experimental observations, confirming that tumour aggregations are not moving if the ECM fibres are distributed randomly, and they only move when the ECM fibres are highly aligned. Moreover, the stationary tumour aggregations can have circular shapes or irregular shapes (with finger-like protrusions), while the moving tumour aggregations have elongate shapes (resembling to clusters, strands or files). We also show that the cell sensing radius impacts tumour shape only when there is a low ratio of fibre to non-fibre ECM components. Finally, we investigate the impact of different ECM fibre orientations corresponding to different tissues, on the overall tumour invasion of these neighbouring tissues.


2020 ◽  
Vol 82 (4) ◽  
Author(s):  
A. A. Malik ◽  
B. Wennberg ◽  
P. Gerlee

Abstract The mechanical properties of the extracellular matrix, in particular its stiffness, are known to impact cell migration. In this paper, we develop a mathematical model of a single cell migrating on an elastic matrix, which accounts for the deformation of the matrix induced by forces exerted by the cell, and investigate how the stiffness impacts the direction and speed of migration. We model a cell in 1D as a nucleus connected to a number of adhesion sites through elastic springs. The cell migrates by randomly updating the position of its adhesion sites. We start by investigating the case where the cell springs are constant, and then go on to assuming that they depend on the matrix stiffness, on matrices of both uniform stiffness as well as those with a stiffness gradient. We find that the assumption that cell springs depend on the substrate stiffness is necessary and sufficient for an efficient durotactic response. We compare simulations to recent experimental observations of human cancer cells exhibiting durotaxis, which show good qualitative agreement.


PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e91875 ◽  
Author(s):  
Yoshihisa Shimizu ◽  
Heike Boehm ◽  
Kazuo Yamaguchi ◽  
Joachim P. Spatz ◽  
Jun Nakanishi

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jacopo Di Russo ◽  
Jennifer L Young ◽  
Julian WR Wegner ◽  
Timmy Steins ◽  
Horst Kessler ◽  
...  

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.


Author(s):  
J. Roemer ◽  
S.R. Simon

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.


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