Decoding tissue mechanical heterogeneity through the integration of biomechanical imaging and single-cell spatial transcriptomics

The mechanical microenvironment profoundly influences cell behavior, tissue organization, and disease progression. Recent advances in biomechanical imaging and single-cell multi-omics technologies have enabled the exploration of tissue heterogeneity from both physical and molecular perspectives. This review summarizes key biomechanical imaging methods and evaluates their capabilities and limitations. We further discuss computational strategies for predicting mechanical properties and highlight integrative approaches that link these predictions with single-cell/spatial omics data. These integrative strategies will pave the way for mechanobiology-informed precision medicine.