Eph-ephrin-mediated differential persistence as a mechanism for cell sorting

Fuente: arXiv
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Auteurs principaux: Bothe, Marius, Lardet, Eloise, Poliakov, Alexei, Pruessner, Gunnar, Bertrand, Thibault, Bordeu, Ignacio
Format: Preprint
Publié: 2025
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author Bothe, Marius
Lardet, Eloise
Poliakov, Alexei
Pruessner, Gunnar
Bertrand, Thibault
Bordeu, Ignacio
author_facet Bothe, Marius
Lardet, Eloise
Poliakov, Alexei
Pruessner, Gunnar
Bertrand, Thibault
Bordeu, Ignacio
contents The phenomenon of cell sorting/segregation, by which cells organise spatially into clusters of specific cell type or function, is essential for tissue morphogenesis. This self-organization process involves an interplay between mechanical, biochemical, and cellular mechanisms that act across various spatial and temporal scales. Several mechanisms for cell sorting have been proposed; however, the physical nature of these mechanisms and how they lead to symmetric or asymmetric cell sorting remains unclear. Here, using experimental data from cocultures of genetically modified Human Embryonic Kidney (HEK293) cells and numerical simulations, we show the existence of a cell sorting mechanism based on transient increases in the persistence of motion of cells. This mechanism is activated on cells overexpressing the ephrinB1-related receptor EphB2 after their interaction with cells overexpressing ephrinB1. We show that this mechanism is sufficient to cause cell sorting, breaking the symmetry of the sorting dynamics, and show that the duration of this transient differential persistence state is optimal for enhancing sorting. Furthermore, we show that in combination with other interaction mechanisms, such as changes in direction-also known as contact inhibition of locomotion-and adhesion forces, differential persistence significantly reduces the timescale of sorting. Our findings offer insights into the behaviour of cell mixtures, the relevance of non-reciprocal interactions, and may provide insight into developmental processes and tissue patterning.
format Preprint
id arxiv_https___arxiv_org_abs_2503_13714
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Eph-ephrin-mediated differential persistence as a mechanism for cell sorting
Bothe, Marius
Lardet, Eloise
Poliakov, Alexei
Pruessner, Gunnar
Bertrand, Thibault
Bordeu, Ignacio
Biological Physics
Soft Condensed Matter
The phenomenon of cell sorting/segregation, by which cells organise spatially into clusters of specific cell type or function, is essential for tissue morphogenesis. This self-organization process involves an interplay between mechanical, biochemical, and cellular mechanisms that act across various spatial and temporal scales. Several mechanisms for cell sorting have been proposed; however, the physical nature of these mechanisms and how they lead to symmetric or asymmetric cell sorting remains unclear. Here, using experimental data from cocultures of genetically modified Human Embryonic Kidney (HEK293) cells and numerical simulations, we show the existence of a cell sorting mechanism based on transient increases in the persistence of motion of cells. This mechanism is activated on cells overexpressing the ephrinB1-related receptor EphB2 after their interaction with cells overexpressing ephrinB1. We show that this mechanism is sufficient to cause cell sorting, breaking the symmetry of the sorting dynamics, and show that the duration of this transient differential persistence state is optimal for enhancing sorting. Furthermore, we show that in combination with other interaction mechanisms, such as changes in direction-also known as contact inhibition of locomotion-and adhesion forces, differential persistence significantly reduces the timescale of sorting. Our findings offer insights into the behaviour of cell mixtures, the relevance of non-reciprocal interactions, and may provide insight into developmental processes and tissue patterning.
title Eph-ephrin-mediated differential persistence as a mechanism for cell sorting
topic Biological Physics
Soft Condensed Matter
url https://arxiv.org/abs/2503.13714