In tissue development, wound healing and aberrant cancer progression cell–cell interactions drive
mixing and segregation of cellular composites. However, the exact nature of these interactions is
unsettled. Here we study the dynamics of packed, heterogeneous cellular systems using wound
closure experiments. In contrast to previous cell sorting experiments, we find non-universal
sorting behavior. For example, monolayer tissue composites with two distinct cell types that show
low and high neighbor exchange rates (i.e., MCF-10A & MDA-MB-231) produce segregated
domains of each cell type, contrary to conventional expectation that the construct should stay
jammed in its initial configuration. On the other hand, tissue compounds where both cell types
exhibit high neighbor exchange rates (i.e., MDA-MB-231 & MDA-MB-436) produce highly mixed
arrangements despite their differences in intercellular adhesion strength. The anomalies allude to a
complex multi-parameter space underlying these sorting dynamics, which remains elusive in
simpler systems and theories merely focusing on bulk properties. Using cell tracking data, velocity
profiles, neighborhood volatility, and computational modeling, we classify asymmetric interfacial
dynamics. We indicate certain understudied facets, such as the effects of cell death & division,
mechanical hindrance, active nematic behavior, and laminar & turbulent flow as their potential
drivers. Our findings suggest that further analysis and an update of theoretical models, to capture
the diverse range of active boundary dynamics which potentially influence self-organization, is
warranted.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:85023 |
| Date | 28 April 2023 |
| Creators | Heine, Paul, Lippoldt, Jürgen, Reddy, Gudur Ashrith, Katira, Parag, Käs, Josef A. |
| Publisher | IOP Publishing |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1367-2630, 043034 |
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