Mechanochemical Principles of Epidermal Tissue Dynamics.

How tissue architecture and function emerge during development and what facilitates their resilience and homeostatic dynamics during adulthood is a fundamental question in biology. Biological tissue barriers such as the skin epidermis have evolved strategies that integrate dynamic cellular turnover with high resilience against mechanical and chemical stresses. Interestingly, both dynamic and resilient functions are generated by a defined set of molecular and cell-scale processes, including adhesion and cytoskeletal remodeling, cell shape changes, cell division, and cell movement. These traits are coordinated in space and time with dynamic changes in cell fates and cell mechanics that are generated by contractile and adhesive forces. In this review, we discuss how studies on epidermal morphogenesis and homeostasis have contributed to our understanding of the dynamic interplay between biochemical and mechanical signals during tissue morphogenesis and homeostasis, and how the material properties of tissues dictate how cells respond to these active stresses, thereby linking cell-scale behaviors to tissue- and organismal-scale changes.

On mechanical phase and form.

Epithelial folding is a fundamental biological process that requires epithelial interactions with the underlying mesenchyme. In this issue of Cell, Huycke et al. investigate intestinal villus formation. They discover that water-droplet-like behavior of mesenchymal cells drives their coalescence into uniformly patterned aggregates, which generate forces on the epithelium to initiate folding.

Mechanobiology: Shaping the future of cellular form and function.

Mechanobiology-the field studying how cells produce, sense, and respond to mechanical forces-is pivotal in the analysis of how cells and tissues take shape in development and disease. As we venture into the future of this field, pioneers share their insights, shaping the trajectory of future research and applications.

Mechanical state transitions in the regulation of tissue form and function.

From embryonic development, postnatal growth and adult homeostasis to reparative and disease states, cells and tissues undergo constant changes in genome activity, cell fate, proliferation, movement, metabolism and growth. Importantly, these biological state transitions are coupled to changes in the mechanical and material properties of cells and tissues, termed mechanical state transitions. These mechanical states share features with physical states of matter, liquids and solids. Tissues can switch between mechanical states by changing behavioural dynamics or connectivity between cells. Conversely, these changes in tissue mechanical properties are known to control cell and tissue function, most importantly the ability of cells to move or tissues to deform. Thus, tissue mechanical state transitions are implicated in transmitting information across biological length and time scales, especially during processes of early development, wound healing and diseases such as cancer. This Review will focus on the biological basis of tissue-scale mechanical state transitions, how they emerge from molecular and cellular interactions, and their roles in organismal development, homeostasis, regeneration and disease.

Mechanical forces across compartments coordinate cell shape and fate transitions to generate tissue architecture.

Morphogenesis and cell state transitions must be coordinated in time and space to produce a functional tissue. An excellent paradigm to understand the coupling of these processes is mammalian hair follicle development, which is initiated by the formation of an epithelial invagination-termed placode-that coincides with the emergence of a designated hair follicle stem cell population. The mechanisms directing the deformation of the epithelium, cell state transitions and physical compartmentalization of the placode are unknown. Here we identify a key role for coordinated mechanical forces stemming from contractile, proliferative and proteolytic activities across the epithelial and mesenchymal compartments in generating the placode structure. A ring of fibroblast cells gradually wraps around the placode cells to generate centripetal contractile forces, which, in collaboration with polarized epithelial myosin activity, promote elongation and local tissue thickening. These mechanical stresses further enhance compartmentalization of Sox9 expression to promote stem cell positioning. Subsequently, proteolytic remodelling locally softens the basement membrane to facilitate a release of pressure on the placode, enabling localized cell divisions, tissue fluidification and epithelial invagination into the underlying mesenchyme. Together, our experiments and modelling identify dynamic cell shape transformations and tissue-scale mechanical cooperation as key factors for orchestrating organ formation.