Quantitative Nanomechanical Analysis of Small Extracellular Vesicles for Tumor Malignancy Indication.

The nanomechanical properties of tumor-derived small extracellular vesicles (sEVs) are essential to cancer progression. Here, nanoindentation is utilized on atomic force microscopy (AFM) to quantitatively investigate the nanomechanical properties of human breast cancer cell-derived sEVs at single vesicle level and explore their relationship with tumor malignancy and vesicle size. It is demonstrated that the stiffness of the sEVs results from the combined contribution of the bending modulus and osmotic pressure of the sEVs. The stiffness and osmotic pressure increase with increasing malignancy of the sEVs and decrease with increasing size of the sEVs. The bending modulus decreases with increasing malignancy of the sEVs and is lower in smaller sEVs. This study builds relationship between the nanomechanical signature of the sEV and tumor malignancy, adding information for better understanding cancer mechanobiology.