support for cells but also provides a train of biochemical and biophysical cues to regulate cell behaviors and trigger tissue functions. [2] An in-depth understanding of the evolution of cell microenvironment over time and modeling of this dynamic microenvironment are essential for tissue regeneration. Biomimetic materials with time-modulated properties, that is, 4D biomimetic materials, have drawn increasing attention due to their bionic nature. Triggered by external stimuli (e.g., temperature, light, electricity, and magnetic field), 4D biomimetic materials exhibit specific changes of their own characteristics, such as mechanical property, hydrophobic/hydrophilic property, redox state, and conformation of surface ligands, to build a dynamic cell microenvironment. [3] However, most existing 4D bionic systems need external stimuli, which is inconvenient for patients, and may limit their clinical transformation. Recently, researchers found that there is a bi-directional interaction between cells and ECM. [4] Specifically, cells do not merely respond passively to biochemical and biophysical signals that are delivered to them. [5] Instead, many cells actively alter their surrounding environment to suit their needs, including soluble factor secretion and matrix deposition, degradation, and reorganization. [6] Among them, the mechanical interaction between cells and substrates has been widely studied, mainly focusing on the regulation of cell adhesion and behavior by stiffness of the substrate, as well as the reorganization of the substrate morphology by cell traction. [7] However, the dynamic interactions between cells and substrates at different stages are rarely studied. Moreover, how this dynamic process directs cells behaviors remains relatively unexplored.In this work, we fabricated a piezoelectric fibrous network with mechanical stiffness similar to that of collagen and applied this network to elucidate the dynamic mechanical interaction between cells and substrates. Mature focal adhesion (FA) is one of the necessary conditions for cell-substrate bi-directional mechanical perception. Thus, the whole process involves two distinct stages: i) "slippage". Before the formation of mature FAs, cells and substrate do not perceive each other's mechanical behaviors, thereby cell activity causes relative slippage of the cells to the substrate without causing nanofiber deformation (Video S1, Supporting Information); and ii) "traction". After the formation of mature FAs, the intracellular biophysical Electromechanical interaction of cells and extracellular matrix are ubiquitous in biological systems. Understanding the fundamentals of this interaction and feedback is critical to design next-generation electroactive tissue engineering scaffold. Herein, based on elaborately modulating the dynamic mechanical forces in cell microenvironment, the design of a smart piezoelectric scaffold with suitable stiffness analogous to that of collagen for on-demand electrical stimulation is reported. Specifically, it generated a piezoele...