A variety of cells are subject to mechanical stretch in vivo, which plays a critical role in the function and homeostasis of cells, tissues, and organs. Deviations from the physiologically relevant mechanical stretch are often associated with organ dysfunction and various diseases. Although mechanical stretch is provided in some in vitro cell culture models, the effects of stretch dimensionality on cells are often overlooked and it remains unclear whether and how stretch dimensionality affects cell behavior. Here we develop cell culture platforms that provide 1-D uniaxial, 2-D circumferential, or 3-D radial mechanical stretches, which recapitulate the three major types of mechanical stretches that cells experience in vivo. We investigate the behavior of human microvascular endothelial cells and human alveolar epithelial cells cultured on these platforms, showing that the mechanical stretch influences cell morphology and cell–cell and cell–substrate interactions in a stretch dimensionality-dependent manner. Furthermore, the endothelial and epithelial cells are sensitive to the physiologically relevant 2-D and 3-D stretches, respectively, which could promote the formation of endothelium and epithelium. This study underscores the importance of recreating the physiologically relevant mechanical stretch in the development of in vitro tissue/organ models.

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