Linear and nonlinear mechanical responses of cell monolayers under crowding

Epithelial monolayers play an important role in a broad range of physiological and pathological processes, such as embryonic development and wound healing. Epithelial monolayers become crowded during cell proliferation and growth, however, their mechanical properties entities remain obscure. This paper presents a novel and efficient method utilizing the structural stiffness matrix-based computational method (SMM) to investigate the mechanical characteristics of an epithelial monolayer as it undergoes varying degrees of crowding. Both D1-type extrusion, representing the extrusion of live cells, and D2-type extrusion, describing the extrusion of apoptotic cells, are examined. Our simulations reveal that the epithelial monolayer exhibits linear elastic behavior under slight crowding and nonlinear elastic behavior in response to overcrowding. These mechanical properties are significantly influenced by the strength of cellular cytoskeleton and the mode of cell extrusion. Moreover, our analysis indicates that the linear deformation of these monolayers is predominantly born by the variation in cell orientation, while the nonlinear deformation originates from the existence of the microtubules. This study further deepens our understanding of the relationship between the mechanical properties of cytoskeleton, individual cells and their monolayers, and may shed light on linking cell behavior to the patterning and morphogenesis of tissues.