Topological Excitations govern Ordering Kinetics in Endothelial Cell Layers

Abstract

Many physiological processes, such as the shear flow alignment of endothelial cells in the vasculature, depend on the transition of cell layers between disordered and ordered phases. Here, we demonstrate that such a transition is driven by the non-monotonic evolution of nematic topological defects and the emergence of topological strings that bind the defects together, unveiling an intermediate phase of ordering kinetics in biological matter. We used time-resolved large-scale imaging and physical modeling to resolve the nature of the non-monotonic decrease in the number of defect pairs. The interaction of the intrinsic cell layer activity and the alignment field determines the occurrence of defect domains, which defines the nature of the transition. Defect pair annihilation is mediated by topological strings spanning multicellular scales within the cell layer. We propose that these long-range interactions in the intermediate ordering phase have significant implications for a wide range of biological phenomena in morphogenesis, tissue remodeling, and disease progression.