Biomechanical approaches for studying integration of tissue structure and function in mammary epithelia

The structure and function of each individual mammary epithelial cell (MEC) is largely controlled by a bidirectional interchange of chemical and mechanical signals with the microenvironment. Most of these signals are tissue-specific, since they arise from the three-dimensional (3D) tissue organization and are modulated during mammary gland development, maturation, pregnancy, lactation, and involution. Although the important role played by structural and mechanical signals in mammary cell and tissue function is being increasingly recognized, quantitative biomechanical approaches are still scarce. Here we review currently available biomechanical tools that allow quantitative examination of individual cells, groups of cells or full monolayers in two-dimensional cultures, and cells in 3D cultures. Current technological limitations and challenges are discussed, with special emphasis on their potential applications in MEC biology. We argue that the combination of biomechanical tools with current efforts in mathematical modeling and in cell and molecular biology applied to 3D cultures provides a powerful approach to unravel the complexity of tissue-specific structure-function relationships.