scholarly journals Model-Based Prediction of an Effective Adhesion Parameter Guiding Multi-Type Cell Segregation

Entropy ◽  
2021 ◽  
Vol 23 (11) ◽  
pp. 1378
Author(s):  
Philipp Rossbach ◽  
Hans-Joachim Böhme ◽  
Steffen Lange ◽  
Anja Voss-Böhme

The process of cell-sorting is essential for development and maintenance of tissues. Mathematical modeling can provide the means to analyze the consequences of different hypotheses about the underlying mechanisms. With the Differential Adhesion Hypothesis, Steinberg proposed that cell-sorting is determined by quantitative differences in cell-type-specific intercellular adhesion strengths. An implementation of the Differential Adhesion Hypothesis is the Differential Migration Model by Voss-Böhme and Deutsch. There, an effective adhesion parameter was derived analytically for systems with two cell types, which predicts the asymptotic sorting pattern. However, the existence and form of such a parameter for more than two cell types is unclear. Here, we generalize analytically the concept of an effective adhesion parameter to three and more cell types and demonstrate its existence numerically for three cell types based on in silico time-series data that is produced by a cellular-automaton implementation of the Differential Migration Model. Additionally, we classify the segregation behavior using statistical learning methods and show that the estimated effective adhesion parameter for three cell types matches our analytical prediction. Finally, we demonstrate that the effective adhesion parameter can resolve a recent dispute about the impact of interfacial adhesion, cortical tension and heterotypic repulsion on cell segregation.

2012 ◽  
Vol 23 (01) ◽  
pp. 93-126 ◽  
Author(s):  
GREG LEMON ◽  
JOHN R. KING

This paper presents a mathematical model to describe the sorting of two different types of cells, arising from differential adhesion mechanisms within biological tissue. The model is based on a continuum approach that takes into account individual cell behavior including aspects of the cell-migration process, dynamics of the adhesions between contacting cells, and finite cell size. Numerical solutions and bifurcation analyses for the case of a collection of two different cell types show a variety of behaviors observed in experiments, including spatially uniform mixing of cells and the formation of two distinct, containing both types of cells or just one. The mathematical model, which is in the form of a set of functional differential equations, represents a novel approach to continuum modeling of cell sorting and migration within biological tissue.


Development ◽  
1988 ◽  
Vol 103 (1) ◽  
pp. 37-48
Author(s):  
W.A. Thomas ◽  
J. Yancey

Embryonic chick neural retina cells possess two classes of adhesion mechanism, one Ca2+-independent, one Ca2+-dependent, responsible for short-term cell aggregation. This study investigates the role of these mechanisms in the long-term cell sorting potentially relevant to in vivo histogenesis. Retina cells are prepared either with both (E cells) or with only one mechanism (TC cells, CD; LTE cells, CI), respectively. The two types of cell preparations are differentially labelled using fluorescein or rhodamine isothiocyanate, mixed and allowed to aggregate in the presence or absence of cycloheximide at 0.5 microgram ml-1 to retard metabolic recovery of the removed adhesive mechanism. When observed by fluorescence and phase-contrast microscopy, the aggregates formed in cycloheximide show cell sorting, the cells with both mechanisms assuming a more interior position relative to those with a single adhesion mechanism. In parallel hanging-drop experiments, preformed aggregates of cells with a single adhesion mechanism are seen to spread upon aggregates of cells with both mechanisms. No sorting occurs amongst cells from a given stage prepared using any single dissociation protocol. The observed cell sorting would thus seem to derive exclusively from differential cell adhesiveness dependent upon the different dissociation conditions and maintained in the presence of cycloheximide. The experiments support the hypothesis that the dual CI and CD adhesion mechanisms in question can play a central role in governing cell-sorting behaviour during normal histogenesis.


2020 ◽  
Vol 67 ◽  
pp. 1-15
Author(s):  
Luis Almeida ◽  
Kevin Atsou ◽  
Marta Marulli ◽  
Diane Peurichard ◽  
Rémi Tesson

We study a model of cell segregation in a population composed of two cell types. Starting from a model initially proposed in [3], we aim to understand the impact of a cell division process on the system’s segregation abilities. The original model describes a population of spherical cells interacting with their close neighbors by means of a repulsion potential and which centers are subject to Brownian motion. Here, we add a stochastic birth-death process in the agent-based model, that approaches a logistic growth term in the continuum limit. We address the linear stability of the spatially homogeneous steady states of the macroscopic model and obtain a precise criterion for the phase transition, which links the system segregation ability to the model parameters. By comparing the criterion with the one obtained without logistic growth, we show that the system’s segregation ability is the result of a complex interplay between logistic growth, diffusion and mechanical repulsive interactions. Numerical simulations are presented to illustrate the results obtained at the microscopic scale.


2018 ◽  
Author(s):  
Simon Brayford ◽  
Eduardo Serna-Morales ◽  
Andrei Luchici ◽  
Toru Hiratsuka ◽  
Brian M. Stramer

SummaryInteractions between different cell-types can induce distinct contact inhibition of locomotion (CIL) responses that are hypothesized to control population-wide behaviors during embryogenesis [1, 2]. However, our understanding of the signals that lead to cell-type specific repulsion, and the precise capacity of heterotypic CIL responses to drive emergent behaviors is lacking. Using a new in vitro model of heterotypic CIL between epithelial and mesenchymal cells, we show that fibrosarcoma cells (HT1080), but not fibroblasts (NIH3T3), are actively repelled by epithelial cells in culture. We show that knocking down EphB2 in fibrosarcoma cells specifically leads to disruption of the repulsion phase of CIL in response to interactions with epithelial cells. Furthermore, this heterotypic interaction requires ERK activation, downstream of EphB2 signaling. We also examine the population-wide effects when these various cell combinations, and their specific heterotypic CIL responses, are allowed to interact in culture. Mixtures of fibrosarcoma and epithelial cells – unlike fibroblasts and epithelial cells – lead to complete sorting and segregation of the two populations, and inhibiting their distinct CIL response by knocking down EphB2 or ERK in fibrosarcoma cells disrupts this emergent sorting behavior. Our understanding of the mechanisms underlying developmental behaviors such as cell sorting is lacking as predominant sorting hypotheses, such as differential adhesion, have recently been found inadequate in predicting the sorting of mesenchymal cells [3, 4]. These data suggest that heterotypic CIL responses, in conjunction with processes such as differential adhesion, may aid the sorting of cell populations during embryogenesis.


1979 ◽  
Vol 38 (1) ◽  
pp. 249-266
Author(s):  
A. Nicol ◽  
D.R. Garrod

It has been reported previously that sorting out of chick embryonic liver parenchyma and limb bud mesenchymal cells would take place in monolayer culture. The distribution of cell types obtained (liver formed the internal, discontinuous phase) was interpreted in terms of the differential adhesion hypothesis. It was suggested that, in monolayer, liver cells were more cohesive than limb bud cells. In this paper we set out to extend the previous observations with 2 particular questions in mind: (i) Is sorting out in monolayer a general phenomenon occurring between a wider range of cell types? (ii) Can evidence be provided for or against the interpretation of results in terms of the differential adhesion hypothesis? Sorting-out experiments were conducted on circular hydrophilic islands, on an otherwise hydrophobic substratum. Under these conditions, sorting-out in monolayer was obtained with binary combinations of 4 chick embryonic tissue types: liver parenchyma, limb bud mesenchyme, pigmented epithelium of the eye and corneal epithelium. With every combination but one, the cells of one type surrounded the cells of the other type, generating what we have called a ‘circle-within-a-circle’ configuration. With the remaining combination, liver parenchyma and corneal epithelium, only localized sorting was obtained. The ‘circle-within-a-circle’ configuration is consistent with an interpretation in terms of the differential adhesion hypothesis, according to which the distribution of cells is determined by the relative strengths of cohesions between their lateral surfaces. In direct support of this is the finding from plating the different cell types at sub-confluent density on hydrophilic substrata that limb bud is the cell tye having the weakest lateral cohesion in monolayer. Limb bud surrounded the other 3 tissues on hydrophilic island. A hierachy of lateral cohesiveness between the 4 cell types has been constructed. It is unlikely that the results can be explained in terms of specific cohesion. When plated together at subconfluent density, the 3 epithelial cell types aggregate together to form mixed monolayered islands, suggesting that they share common adhesive mechanisms.


2017 ◽  
Vol 5 (4) ◽  
pp. 27
Author(s):  
Huda Arshad ◽  
Ruhaini Muda ◽  
Ismah Osman

This study analyses the impact of exchange rate and oil prices on the yield of sovereign bond and sukuk for Malaysian capital market. This study aims to ascertain the effect of weakening Malaysian Ringgit and declining of crude oil price on the fixed income investors in the emerging capital market. This study utilises daily time series data of Malaysian exchange rate, oil price and the yield of Malaysian sovereign bond and sukuk from year 2006 until 2015. The findings show that the weakening of exchange rate and oil prices contribute different impacts in the short and long run. In the short run, the exchange rate and oil prices does not have a direct relation with the yield of sovereign bond and sukuk. However, in the long run, the result reveals that there is a significant relationship between exchange rate and oil prices on the yield of sovereign bond and sukuk. It is evident that only a unidirectional causality relation is present between exchange rate and oil price towards selected yield of Malaysian sovereign bond and sukuk. This study provides numerical and empirical insights on issues relating to capital market that supports public authorities and private institutions on their decision and policymaking process.


2020 ◽  
Vol 19 (6) ◽  
pp. 1015-1034
Author(s):  
O.Yu. Patrakeeva

Subject. The paper considers national projects in the field of transport infrastructure, i.e. Safe and High-quality Roads and Comprehensive Plan for Modernization and Expansion of Trunk Infrastructure, and the specifics of their implementation in the Rostov Oblast. Objectives. The aim is to conduct a statistical assessment of the impact of transport infrastructure on the region’s economic performance and define prospects for and risks of the implementation of national infrastructure projects in conditions of a shrinking economy. Methods. I use available statistics and apply methods and approaches with time-series data, namely stationarity and cointegration tests, vector autoregression models. Results. The level of economic development has an impact on transport infrastructure in the short run. However, the mutual influence has not been statistically confirmed. The paper revealed that investments in the sphere of transport reduce risk of accidents on the roads of the Rostov Oblast. Improving the quality of roads with high traffic flow by reducing investments in the maintenance of subsidiary roads enables to decrease accident rate on the whole. Conclusions. In conditions of economy shrinking caused by the complex epidemiological situation and measures aimed at minimizing the spread of coronavirus, it is crucial to create a solid foundation for further economic recovery. At the government level, it is decided to continue implementing national projects as significant tools for recovery growth.


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