Xingbo Yang

Motility-driven glass and jamming transitions in biological tissues

Cell motion inside dense tissues governs many biological processes, including embryonic development and cancer metastasis, and recent experiments suggest that these tissues exhibit collective glassy behavior. To make quantitative predictions about glass transitions in tissues, we study a self-propelled Voronoi (SPV) model that simultaneously captures polarized cell motility and multi-body cell-cell interactions in a confluent tissue, where there are no gaps between cells. We demonstrate that the model exhibits a jamming transition from a solid-like state to a fluid-like state that is controlled by three parameters: the single-cell motile speed, the persistence time of single-cell tracks, and a target shape index that characterizes the competition between cell-cell adhesion and cortical tension. In contrast to traditional particulate glasses, we are able to identify an experimentally accessible structural order parameter that specifies the entire jamming surface as a function of model parameters. We demonstrate that a continuum Soft Glassy Rheology model precisely captures this transition in the limit of small persistence times, and explain how it fails in the limit of large persistence times. These results provide a framework for understanding the collective solid-to-liquid transitions that have been observed in embryonic development and cancer progression, which may be associated with Epithelial-to-Mesenchymal transition in these tissues.

Spiral and never-settling patterns in active systems.

We present a combined numerical and analytical study of pattern formation in an active system where particles align, possess a density-dependent motility, and are subject to a logistic reaction. The model can describe suspensions of reproducing bacteria, as well as polymerizing actomyosin gels in vitro or in vivo. In the disordered phase, we find that motility suppression and growth compete to yield stable or blinking patterns, which, when dense enough, acquire internal orientational ordering to give asters or spirals. We predict these may be observed within chemotactic aggregates in bacterial fluids. In the ordered phase, the reaction term leads to previously unobserved never-settling patterns which can provide a simple framework to understand the formation of motile and spiral patterns in intracellular actin systems.

Correlating cell shape and cellular stress in motile confluent tissues

Significance Using a self-propelled Voronoi model of epithelia known to predict a liquid–solid transition, we examine the interplay between cell motility and cell shape, tuned by cortex contractility and cell–cell adhesion, in controlling the mechanical properties of tissue. Our work provides a unifying framework for existing, seemingly distinct notions of stress in tissues and relates stresses to material properties. In particular, we show that the temporal correlation function of shear stresses can be used to define an effective tissue viscosity that diverges at the liquid–solid transition. This finding suggests a unique way of analyzing traction force microscopy data that may provide information on tissue rheology. Collective cell migration is a highly regulated process involved in wound healing, cancer metastasis, and morphogenesis. Mechanical interactions among cells provide an important regulatory mechanism to coordinate such collective motion. Using a self-propelled Voronoi (SPV) model that links cell mechanics to cell shape and cell motility, we formulate a generalized mechanical inference method to obtain the spatiotemporal distribution of cellular stresses from measured traction forces in motile tissues and show that such traction-based stresses match those calculated from instantaneous cell shapes. We additionally use stress information to characterize the rheological properties of the tissue. We identify a motility-induced swim stress that adds to the interaction stress to determine the global contractility or extensibility of epithelia. We further show that the temporal correlation of the interaction shear stress determines an effective viscosity of the tissue that diverges at the liquid–solid transition, suggesting the possibility of extracting rheological information directly from traction data.