Small-scale demixing in confluent biological tissues. Issue 13 (20th March 2020)

• Record Type: Journal Article
• Authors: Sahu, Preeti; Sussman, Daniel M.; Rübsam, Matthias; Mertz, Aaron F.; Horsley, Valerie; Dufresne, Eric R.; Niessen, Carien M.; Marchetti, M. Cristina; Manning, M. Lisa; Schwarz, J. M.
• Is Part Of: Soft matter. Volume 16:Issue 13(2020)
• Page Start: 3325
• Page End: 3337
• Publication Date: 2020-03-20
• Subjects: Soft condensed matter -- Periodicals; 530.413
• DOI: 10.1039/c9sm01084j
• Languages: English
• ISSNs: 1744-683X

Abstract

Abstract : While interfacial tension in confluent cellular mixtures leads to large-scale demixing, cell shape disparity leads to robust small-scale demixing that is observed in experiments and can be explained via neighbor exchange barriers at an interface. Abstract : Surface tension governed by differential adhesion can drive fluid particle mixtures to sort into separate regions, i.e., demix. Does the same phenomenon occur in confluent biological tissues? We begin to answer this question for epithelial monolayers with a combination of theory via a vertex model and experiments on keratinocyte monolayers. Vertex models are distinct from particle models in that the interactions between the cells are shape-based, as opposed to distance-dependent. We investigate whether a disparity in cell shape or size alone is sufficient to drive demixing in bidisperse vertex model fluid mixtures. Surprisingly, we observe that both types of bidisperse systems robustly mix on large lengthscales. On the other hand, shape disparity generates slight demixing over a few cell diameters, a phenomenon we term micro-demixing. This result can be understood by examining the differential energy barriers for neighbor exchanges (T1 transitions). Experiments with mixtures of wild-type and E-cadherin-deficient keratinocytes on a substrate are consistent with the predicted phenomenon of micro-demixing, which biology may exploit to create subtle patterning. The robustness of mixing at large scales, however, suggests that despite some differences in cell shape and size, progenitor cells can readily mix throughout a developing tissue until acquiring means of recognizing cells of different types.