Biocompatible Optically Transparent MEMS for Micromechanical Stimulation and Multimodal Imaging of Living Cells.

Cells and tissues in our body are continuously subjected to mechanical stress. Mechanical stimuli, such as tensile and contractile forces, and shear stress, elicit cellular responses, including gene and protein alterations that determine key behaviors, including proliferation, differentiation, migration, and adhesion. Several tools and techniques have been developed to study these mechanobiological phenomena, including micro-electro-mechanical systems (MEMS). MEMS provide a platform for nano-to-microscale mechanical stimulation of biological samples and quantitative analysis of their biomechanical responses. However, current devices are limited in their capability to perform single cell micromechanical stimulations as well as correlating their structural phenotype by imaging techniques simultaneously. In this study, a biocompatible and optically transparent MEMS for single cell mechanobiological studies is reported. A silicon nitride microfabricated device is designed to perform uniaxial tensile deformation of single cells and tissue. Optical transparency and open architecture of the device allows coupling of the MEMS to structural and biophysical assays, including optical microscopy techniques and atomic force microscopy (AFM). We demonstrate the design, fabrication, testing, biocompatibility and multimodal imaging with optical and AFM techniques, providing a proof-of-concept for a multimodal MEMS. The integrated multimodal system would allow simultaneous controlled mechanical stimulation of single cells and correlate cellular response.

Atomic force microscopy reveals age-dependent changes in nanomechanical properties of the extracellular matrix of native human menisci: implications for joint degeneration and osteoarthritis.

With aging, the menisci become more susceptible to degeneration due to sustained mechanical stress accompanied by age-related changes in the extracellular matrix (ECM). However, the mechanistic relationship between age-related meniscal degeneration and osteoarthritis (OA) development is not yet fully understood. We have examined the nanomechanical properties of the ECM of normal, aged, and degenerated human menisci using atomic force microscopy (AFM). Elasticity maps of the ECM revealed a unique differential qualitative nanomechanical profile of healthy young tissue: prominent unimodal peaks in the elastic moduli distribution in each region (outer, middle, and inner). Healthy aged tissue showed similar regional elasticity but with both unimodal and bimodal distributions that included higher elastic moduli. In contrast, degenerated OA tissue showed the broadest distribution without prominent peaks indicative of substantially increased mechanical heterogeneity in the ECM. AFM analysis reveals distinct regional nanomechanical profiles that underlie aging-dependent tissue degeneration and OA. FROM THE CLINICAL EDITOR: The authors of this study used atomic force microscopy to determine the nanomechanical properties of the extracellular matrix in normal and degenerated human menisci, as well as in menisci undergoing healthy aging. Comparison of these properties help to understand the relationship between healthy ageing, and age-dependent joint degeneration and osteoarthritis.