Provided are methods for detecting and treating disease states, including cancer, diabetes, fibrosis, and autoimmune diseases, by detecting increased mechanical modulus, or stiffness, or targeting tissues having increased mechanical modulus, or stiffness. Practicing these methods provides specific and localized detection assays and therapies for these disease states. Provided are mechano-responsive cell systems that can selectively detect and treat cancer metastases by targeting the unique biophysical and mechanical properties in the tumor microenvironment. Provided are methods for making mechano-sensitive CAR T cells by using mechano-responsive promoter logic. Provided are blood tests using engineered stem cells that express reporters after the cells home to a specific niche and secrete the reporter into the blood, which can be then be detected with a blood test. In alternative embodiments, provided are ultrasensitive detection platforms, able to detect target molecules or cells in blood with single-molecule
