Sparse mesenchymal cell networks as a fluid under tension

Abstract

Sparse mesenchymal cellular networks are ubiquitous across animals, shaping both embryonic and adult structures through dynamic interactions with epithelia. Yet, the physical principles underlying their collective behaviors remain elusive, as their stellate cells and large extracellular spaces - filled with matrix or interstitial fluid - pose significant experimental and computational challenges. Here, we demonstrate that the avian presomitic mesoderm (PSM), a canonical embryonic mesenchymal tissue, behaves as a fluid under tension, exhibiting structural organization that cannot be explained by simple Brownian-like cell motion. Through quantitative modeling, we identify contact inhibition of locomotion (CIL) - where cells actively retract and move away upon contact - as a key mechanism that enables sparse mesenchymal networks to sustain macroscopic tension while flowing like a fluid. Consistent with this mechanism, colliding PSM cells turn away from each other, and spreading PSM explants accelerate outward as interior voids open. Simple continuum equations relate observable cell-scale parameters to the emergent remodeling dynamics observed in both experiments and simulations. Together, these findings put forward an unrecognized mechanical role for CIL, extending its influence beyond collective migration, and establish the fluid-under-tension state as a distinct class of tissue behavior that describes key developing embryonic tissues and may illuminate how matrix-rich adult tissues fluidize during tumorigenesis.

Abstract as supplied by the indexing source. © the authors / publisher.