The extracellular matrix (ECM) constituting the microenvironment of a tissue is a collection of proteins, glycoproteins, and proteoglycans. Composed of varying ratios of these molecules, the ECM in tissues or organs possesses different chemical and physical properties. In the ECM microenvironment of a tissue or organ, cell regulation is coordinated by both chemical and physical cues of the surrounding ECM to direct cell activities, such as adhesion, migration, proliferation, and differentiation.^1,2  In particular, physical cues including geometry, topography, and mechanics have been shown to direct tissue formation during development and maintain tissue homeostasis throughout the postnatal life.^1,3  For example, during embryo development, ECM mechanics plays an important role in germ layer organization⁴  and gastrulation.⁵  In the postnatal life, cells in a healthy tissue continue to receive mechanical cues from the ECM to regulate tissue homeostasis whereas during tumor formation or disease progression, abnormal ECM deposition or cross-linking alters stiffness of the ECM, which in turn changes mechanical cues to disrupt tissue homeostasis, ultimately leading to malignancy.⁶  Recently, emerging research findings of stem cell studies have demonstrated that lineage differentiation of embryonic stem cells (ESCs) is affected by mechanical properties of their surrounding environment.⁷  Stiffness of the ECM, independently of biochemical cues, was identified as a critical environmental factor capable of directing lineage-specific differentiation of adult stem cells.⁸  These research findings collectively suggest that ECM mechanics plays an important role in regulation of cell activities.