Cell-matrix interactions, mediated by cellular force and matrix remodeling, result in a dynamic reciprocity that drives numerous biological processes and disease progression. Currently, there is no available method for direct quantification cell traction force and matrix remodeling in 3D matrices as a function of time. To address this long-standing need, we recently developed a high-resolution microfabricated sensor1 that measures cell force, tissue-stiffness and can apply mechanical stimulation to the tissue. Here the tissue self-assembles and self-integrates with the sensor. With primary fibroblasts, cancer cells and neurons, we demonstrated the feasibility of the sensor by measuring single/multiple cell force with a resolution of 1 nN, and tissue stiffness1 due to matrix remodeling by the cells. The sensor can be translated into a high-throughput system for clinical assays such as patient-specific drug and phenotypic screening. In this paper, we present the detailed protocol for manufacturing the sensors, preparing experimental setup, developing assays with different tissues, and for imaging and analyzing the data.