Multicellular Rosettes Drive Fluid-solid Transition in Epithelial Tissues

Abstract

Models for confluent biological tissues often describe the network formed by cells as a triple-junction network, similar to foams. However, higher-order vertices or multicellular rosettes are prevalent in developmental and in vitro processes and have been recognized as crucial in many important aspects of morphogenesis, disease, and physiology. In this work, we study the influence of rosettes on the mechanics of a confluent tissue. We find that the existence of rosettes in a tissue can greatly influence its rigidity. Using a generalized vertex model and the effective medium theory, we find a fluid-to-solid transition driven by rosette density and intracellular tensions. This transition exhibits several hallmarks of a second-order phase transition such as a growing correlation length and a universal critical scaling in the vicinity of a critical point. Furthermore, we elucidate the nature of rigidity transitions in dense biological tissues and other cellular structures using a generalized Maxwell constraint counting approach, which answers a long-standing puzzle of the origin of solidity in these systems.

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Plain Language Summary

Every organ in the human body is lined with epithelial cells. The cells in these tissues are normally sedentary or solidlike but become migratory or fluidlike during embryonic development, tissue repair, and cancer invasion. Researchers do not understand this striking transition from stationary to active behaviors, which could help shed light on various aspects of biology, medicine, and disease progression. We develop a theoretical model of cellular organization in these tissues that takes into account more complex junctions between cells than previous models—junctions that provide insight into this stark difference in cell behavior.

A common assumption in cellular models is that a tissue always looks like a foam network, consisting of only triple junctions where three cells meet. However, cellular rosettes, where five or more cells meet at a single point, are prevalent in nature. Our generalized theoretical framework takes into account the presence of rosettes. We find that the tissue can behave as a solid or a fluid depending on the number of rosettes present as well as the mechanical tension forces in cell junctions. We also make experimentally testable predictions regarding the strong correlations and the interplay between cellular topology and mechanical tensions in a tissue.

From a physics perspective, the transformation between fluid and solid states exhibits many hallmarks of a second-order phase transition, such as a growing correlation length and universal scaling relations near the critical point. We elucidate the nature and origin of rigidity transition in tissue with a generalized theory that offers a unifying perspective of tissue mechanics.