scholarly journals Active inter-cellular forces in collective cell motility

2020 ◽  
Vol 17 (169) ◽  
pp. 20200312
Author(s):  
Guanming Zhang ◽  
Romain Mueller ◽  
Amin Doostmohammadi ◽  
Julia M. Yeomans

The collective behaviour of confluent cell sheets is strongly influenced both by polar forces, arising through cytoskeletal propulsion, and by active inter-cellular forces, which are mediated by interactions across cell-cell junctions. We use a phase-field model to explore the interplay between these two contributions and compare the dynamics of a cell sheet when the polarity of the cells aligns to (i) their main axis of elongation, (ii) their velocity and (iii) when the polarity direction executes a persistent random walk. In all three cases, we observe a sharp transition from a jammed state (where cell rearrangements are strongly suppressed) to a liquid state (where the cells can move freely relative to each other) when either the polar or the inter-cellular forces are increased. In addition, for case (ii) only, we observe an additional dynamical state, flocking (solid or liquid), where the majority of the cells move in the same direction. The flocking state is seen for strong polar forces, but is destroyed as the strength of the inter-cellular activity is increased.

Author(s):  
Kenichi Nagase ◽  
Jun Kobayashi ◽  
Teruo Okano

Temperature-responsive intelligent surfaces, prepared by the modification of an interface with poly( N -isopropylacrylamide) and its derivatives, have been used for biomedical applications. Such surfaces exhibit temperature-responsive hydrophilic/hydrophobic alterations with external temperature changes, which, in turn, result in thermally modulated interactions with biomolecules and cells. In this review, we focus on the application of these intelligent surfaces to chromatographic separation and cell cultures. Chromatographic separations using several types of intelligent surfaces are mentioned briefly, and various effects related to the separation of bioactive compounds are discussed, including wettability, copolymer composition and graft polymer architecture. Similarly, we also summarize temperature-responsive cell culture substrates that allow the recovery of confluent cell monolayers as contiguous living cell sheets for tissue-engineering applications. The key factors in temperature-dependent cell adhesion/detachment control are discussed from the viewpoint of grafting temperature-responsive polymers, and new methodologies for effective cell sheet culturing and the construction of thick tissues are summarized.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yoshiyuki Kasai ◽  
Tsunetaro Morino ◽  
Eri Mori ◽  
Kazuhisa Yamamoto ◽  
Hiromi Kojima

Abstract The proliferation and differentiation of cultured epithelial cells may be modified by Rho-associated kinase (ROCK) inhibition and extracellular Ca2+ concentration. However, it was not known whether a combination would influence the behavior of cultured epithelial cells through changes in the phosphorylation of non-muscle myosin light chain II (MLC). Here we show that the combination of ROCK inhibition with Ca2+ elevation regulated the phosphorylation of MLC and improved both cell expansion and cell–cell adhesion during the culture of human nasal mucosal epithelial cell sheets. During explant culture, Ca2+ enhanced the adhesion of nasal mucosal tissue, while ROCK inhibition downregulated MLC phosphorylation and promoted cell proliferation. During cell sheet culture, an elevation of extracellular Ca2+ promoted MLC phosphorylation and formation of cell–cell junctions, allowing the harvesting of cell sheets without collapse. Moreover, an in vitro grafting assay revealed that ROCK inhibition increased the expansion of cell sheets three-fold (an effect maintained when Ca2+ was also elevated), implying better wound healing potential. We suggest that combining ROCK inhibition with elevation of Ca2+ could facilitate the fabrication of many types of cell graft.


2006 ◽  
Vol 53 ◽  
pp. 70-73
Author(s):  
Teruo Okano

In order to avoid several complications resulted from biodegradable scaffolds or single cell injection, we have developed “cell sheet engineering”. Our concept is novel tissue reconstruction not from single cells but from cell sheets. In order to prepare cell sheets, temperature-responsive culture dishes are utilized. Since temperature-responsive polymers are covalently grafted on the dishes, various types of cells adhere and proliferate on them at 37°C, but are spontaneously detached only by reducing temperature below 32°C without any need for proteolytic enzyme. All the confluent cells are noninvasively harvested as a single contiguous cell sheets with intact cell-cell junctions and deposited extracellular matrix. We have utilized these harvested cell sheets for various tissue reconstructions including ocular surfaces, periodontal ligament, cardiac patches as well as bladder.


2021 ◽  
Author(s):  
Guanming Zhang ◽  
Julia Mary Yeomans

We use a computational phase-field model together with analytical analysis to study how inter-cellular active forces can mediate individual cell morphology and collective motion in a confluent cell monolayer. Contractile inter-cellular interactions lead to cell elongation, nematic ordering and active turbulence, characterised by motile topological defects. Extensile interactions result in frustration, and perpendicular cell orientations become more prevalent. Furthermore, we show that contractile behaviour can change to extensile behaviour if anisotropic fluctuations in cell shape are considered.


2021 ◽  
Vol 9 ◽  
Author(s):  
Katsuhiko Sato ◽  
Daiki Umetsu

The vertex model is a useful mathematical model to describe the dynamics of epithelial cell sheets. However, existing vertex models do not distinguish contraction forces on the cell boundary from adhesion between cells, employing a single parameter to express both. In this paper, we introduce the rest length of the cell boundary and its dynamics into the existing vertex model, giving a novel formulation of the model that treats separately the contraction force and the strength of adhesion between cells. We apply this vertex model to the phenomenon of compartment boundary in the fruit fly pupa, recapturing the observation that increasing the strength of adhesion between cells straightens the compartment boundary, even though contraction forces at cell boundaries remain unchanged. We also discuss possibilities of the novel vertex models by considering the stretching of a cell sheet by external forces.


2019 ◽  
Vol 2 (4) ◽  
pp. e201900414 ◽  
Author(s):  
Satoshi Konishi ◽  
Tomoki Yano ◽  
Hiroo Tanaka ◽  
Tomoaki Mizuno ◽  
Hatsuho Kanoh ◽  
...  

The paracellular barrier function of tight junctions (TJs) in epithelial cell sheets is robustly maintained against mechanical fluctuations, by molecular mechanisms that are poorly understood. Vinculin is an adaptor of a mechanosensory complex at the adherens junction. Here, we generated vinculin KO Eph4 epithelial cells and analyzed their confluent cell-sheet properties. We found that vinculin is dispensable for the basic TJ structural integrity and the paracellular barrier function for larger solutes. However, vinculin is indispensable for the paracellular barrier function for ions. In addition, TJs stochastically showed dynamically distorted patterns in vinculin KO cell sheets. These KO phenotypes were rescued by transfecting full-length vinculin and by relaxing the actomyosin tension with blebbistatin, a myosin II ATPase activity inhibitor. Our findings indicate that vinculin resists mechanical fluctuations to maintain the TJ paracellular barrier function for ions in epithelial cell sheets.


2000 ◽  
Author(s):  
G. W. Brodland ◽  
Jim H. Veldhuis ◽  
Daniel I-Li Chen

Abstract Computer simulations and analytical mechanics are used to investigate the mechanics of cell sheets. The simulations are based on a recent finite element formulation [1] in which each cell is modeled using multiple finite elements, and cells can rearrange. Sheet stresses calculated using an analytical expression based on average cell shape are found to agree well with those calculated in the finite element simulations. This is an important step towards the development of constitutive equations to describe real cell sheets.


Author(s):  
R. Stephens ◽  
G. Schidlovsky ◽  
S. Kuzmic ◽  
P. Gaudreau

The usual method of scraping or trypsinization to detach tissue culture cell sheets from their glass substrate for further pelletization and processing for electron microscopy introduces objectionable morphological alterations. It is also impossible under these conditions to study a particular area or individual cell which have been preselected by light microscopy in the living state.Several schemes which obviate centrifugation and allow the embedding of nondetached tissue culture cells have been proposed. However, they all preserve only a small part of the cell sheet and make use of inverted gelatin capsules which are in this case difficult to handle.We have evolved and used over a period of several years a technique which allows the embedding of a complete cell sheet growing at the inner surface of a tissue culture roller tube. Observation of the same cell by light microscopy in the living and embedded states followed by electron microscopy is performed conveniently.


1960 ◽  
Vol XXXIV (I) ◽  
pp. 27-32 ◽  
Author(s):  
Stian Erichsen ◽  
Weiert Velle

ABSTRACT The metabolism of some oestrogenic hormones was studied in vitro by the use of cells grown on a medium free from blood. The methods used for the culture of cells from bovine testis, endometrium, amnion, and liver in confluent cell sheets on glass are described. The interconversion of oestrone and oestradiol-17β was demonstrated in the presence of cells from amnion, endometrium, and also from testicles of young calves and bulls. Only trace amounts of oestrone were found following incubations with oestradiol-17α in these tissues. Bovine liver cells grown in vitro showed a very poor capacity to bring about the interconversion mentioned above.


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