Spatial Characterization of the Human Meniscus: Bridging Biomechanics and Biochemistry Using Atomic Force Microscopy Micro-Indentation and Mass Spectrometry Imaging.

Meniscus biomechanical properties are dependent on the microscale composition and distribution of structural proteins and other macromolecules. In this context, the local mechanical properties (material properties) of the meniscus largely depend on the chemical composition. However, to date, a direct link between the spatial biomechanical and biochemical footprint of the meniscus at the microscale is lacking. To this end, we show a multimodal imaging approach for fresh frozen tissue linking the biomechanical and biochemical readouts from atomic force microscopy (AFM) micro-indentation and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI), respectively. We consecutively applied both imaging modalities on the same tissue section, enabling direct correlative comparison across nano- to micrometer length scales. Using human meniscus cryosections, we provide spatial distribution information of collagen and other proteins in three zones of the meniscus section exhibiting different apparent elasticity. This methodology shows promise in providing a better understanding of the relationship between local meniscus composition and micromechanics. In addition, the technique has potential for improved detection of meniscus degeneration biomarkers and, in the future, linking those to clinical imaging readouts.