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eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yelena Y Bernadskaya ◽  
Haicen Yue ◽  
Calina Copos ◽  
Lionel Christiaen ◽  
Alex Mogilner

Physiological and pathological morphogenetic events involve a wide array of collective movements, suggesting that multicellular arrangements confer biochemical and biomechanical properties contributing to tissue scale organization. The Ciona cardiopharyngeal progenitors provide the simplest model of collective cell migration, with cohesive bilateral cell pairs polarized along the leader-trailer migration path while moving between the ventral epidermis and trunk endoderm. We use the Cellular Potts Model to computationally probe the distributions of forces consistent with shapes and collective polarity of migrating cell pairs. Combining computational modeling, confocal microscopy, and molecular perturbations, we identify cardiopharyngeal progenitors as the simplest cell collective maintaining supracellular polarity with differential distributions of protrusive forces, cell-matrix adhesion, and myosin-based retraction forces along the leader-trailer axis. 4D simulations and experimental observations suggest that cell-cell communication helps establish a hierarchy to align collective polarity with the direction of migration, as observed with three or more cells in silico and in vivo. Our approach reveals emerging properties of the migrating collective: cell pairs are more persistent, migrating longer distances, and presumably with higher accuracy. Simulations suggest that cell pairs can overcome mechanical resistance of the trunk endoderm more effectively when they are polarized collectively. We propose that polarized supracellular organization of cardiopharyngeal progenitors confers emergent physical properties that determine mechanical interactions with their environment during morphogenesis.


2021 ◽  
Vol 8 ◽  
Author(s):  
Vincent Noël ◽  
Marco Ruscone ◽  
Gautier Stoll ◽  
Eric Viara ◽  
Andrei Zinovyev ◽  
...  

WebMaBoSS is an easy-to-use web interface for conversion, storage, simulation and analysis of Boolean models that allows to get insight from these models without any specific knowledge of modeling or coding. It relies on an existing software, MaBoSS, which simulates Boolean models using a stochastic approach: it applies continuous time Markov processes over the Boolean network. It was initially built to fill the gap between Boolean and continuous formalisms, i.e., providing semi-quantitative results using a simple representation with a minimum number of parameters to fit. The goal of WebMaBoSS is to simplify the use and the analysis of Boolean models coping with two main issues: 1) the simulation of Boolean models of intracellular processes with MaBoSS, or any modeling tool, may appear as non-intuitive for non-experts; 2) the simulation of already-published models available in current model databases (e.g., Cell Collective, BioModels) may require some extra steps to ensure compatibility with modeling tools such as MaBoSS. With WebMaBoSS, new models can be created or imported directly from existing databases. They can then be simulated, modified and stored in personal folders. Model simulations are performed easily, results visualized interactively, and figures can be exported in a preferred format. Extensive model analyses such as mutant screening or parameter sensitivity can also be performed. For all these tasks, results are stored and can be subsequently filtered to look for specific outputs. This web interface can be accessed at the address: https://maboss.curie.fr/webmaboss/ and deployed locally using docker. This application is open-source under LGPL license, and available at https://github.com/sysbio-curie/WebMaBoSS.


2021 ◽  
Vol 11 (18) ◽  
pp. 8746
Author(s):  
Jorge Gonzalez-Rico ◽  
Emanuel Nunez-Sardinha ◽  
Leticia Valencia ◽  
Angel Arias ◽  
Arrate Muñoz-Barrutia ◽  
...  

This review focuses on novel applications based on multifunctional materials to actuate biological processes. The first section of the work revisits the current knowledge on mechanically dependent biological processes across several scales from subcellular and cellular level to the cell-collective scale (continuum approaches). This analysis presents a wide variety of mechanically dependent biological processes on nervous system behaviour; bone development and healing; collective cell migration. In the second section, this review presents recent advances in smart materials suitable for use as cell substrates or scaffolds, with a special focus on magneto-active polymers (MAPs). Throughout the manuscript, both experimental and computational methodologies applied to the different treated topics are reviewed. Finally, the use of smart polymeric materials in bioengineering applications is discussed.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kan Zhu ◽  
Nicholas R. Hum ◽  
Brian Reid ◽  
Qin Sun ◽  
Gabriela G. Loots ◽  
...  

2020 ◽  
Vol 20 (4) ◽  
pp. 206-207
Author(s):  
Lucy Bird
Keyword(s):  
T Cell ◽  

2019 ◽  
Author(s):  
D. A. Vargas ◽  
T. Heck ◽  
B. Smeets ◽  
H. Ramon ◽  
H. Parameswaran ◽  
...  

AbstractThe interplay between cell-cell and cell-substrate interactions is complex yet necessary for the formation and well-functioning of tissues. The same mechanosensing mechanisms used by the cell to sense its extracellular matrix, also play a role in intercellular interactions. We used the discrete element method to develop a computational model of a deformable cell that includes subcellular components responsible for mechanosensing. We modeled a cell pair in 3D on a patterned substrate, a simple laboratory setup to study intercellular interactions. We explicitly modeled focal adhesions between the cells and the substrate, and adherens junctions between cells. These mechanosensing adhesions matured; their disassembly rate was dictated by the force they carry. We also modeled stress fibers which bind the discrete adhesions and contract. The mechanosensing fibers strengthened upon stalling and exerted higher forces. Traction exerted on the substrate was used to generate maps displaying the magnitude of the tractions along the cell-substrate interface. Simulated traction maps are compared to experimental maps obtained via traction force microscopy. The model recreates the dependence on substrate stiffness of the tractions’ spatial distribution across the cell-substrate interface, the contractile moment of the cell pair, the intercellular force, and the number of focal adhesions. It also recreates the phenomenon of cell decoupling, in which cells exert forces separately when substrate stiffness increases. More importantly, the model provides viable molecular explanations for decoupling. It shows that the implemented mechanosensing mechanisms are responsible for competition between different fiber-adhesion configurations present in the cell pair. The point at which an increasing substrate stiffness becomes as high as that of the cell-cell interface is the tipping point at which configurations that favor cell-substrate adhesion dominate over those favoring cell-cell adhesion. This competition is responsible for decoupling. Additionally, we learn that extent of decoupling is modulated by adherens junction maturation.Statement of SignificanceCells are sensitive to mechanical factors of their extracellular matrix while simultaneously in contact with other cells. This creates complex intercellular interactions that depend on substrate stiffness and play a role in processes such as development and diseases like cardiac arrhythmia, asthma, and cancer. The simplest cell collective system in vitro is a cell pair on a patterned substrate. We developed a computational model of this system which explains the role of molecular adhesions and contractile fibers in the dynamics of cell-cell interactions on substrates with different stiffness. It is one of the first models of a deformable cell collective based on mechanical principles. It recreates cellular decoupling, a phenomenon in which cells exert forces separately, when substrate stiffness increases.


2019 ◽  
Author(s):  
Julian J.A Hoving ◽  
Elizabeth Harford-Wright ◽  
Patrick Wingfield-Digby ◽  
Anne-Laure Cattin ◽  
Mariana Campana ◽  
...  

AbstractCollective cell migration is fundamental for the development of organisms and in the adult, for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact-inhibition-of-locomotion (CIL), a local repulsive force, propels the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during Schwann cell collective migration, which is required for peripheral nerve regeneration. However, distinct from its role in cell-cell adhesion, the repulsion process is independent of N-cadherin trans-homodimerisation and the associated adherens junction complex. Rather, the extracellular domain of N-cadherin acts to traffic a repulsive Slit2/Slit3 signal to the cell-surface. Inhibiting Slit2/Slit3 signalling inhibits CIL and subsequently collective SC migration, resulting in adherent, non-migratory cell clusters. These findings provide insight into how opposing signals can mediate collective cell migration and how CIL pathways are promising targets for inhibiting pathological cell migration.


ACS Nano ◽  
2018 ◽  
Vol 12 (9) ◽  
pp. 9279-9290 ◽  
Author(s):  
Yue Wu ◽  
Moustafa R. K. Ali ◽  
Bin Dong ◽  
Tiegang Han ◽  
Kuangcai Chen ◽  
...  

2018 ◽  
Vol 121 (1) ◽  
Author(s):  
Hsiang-Ying Chen ◽  
Yi-Teng Hsiao ◽  
Shu-Chen Liu ◽  
Tien Hsu ◽  
Wei-Yen Woon ◽  
...  

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