Fiber-Tip Shear Force Probe for Single-Cell Adhesion Force Measurements

Single-cell adhesion studies play a crucial role in cell biology. Cell adhesion measurement methods, such as atomic force microscopy (AFM) technology, can be used to measure the single-cell adhesion force. However, these methods have many limitations, such as complex operations or the need for labeling. In this study, we proposed a miniature fiber-tip shear force probe (FSFP) that can achieve accurate measurement of the single-cell adhesion force under physiological conditions. A shear force probe structure that facilitates lateral manipulation was designed based on the principles of structural mechanics and fabricated integrally at the end face of a single-mode fiber using femtosecond laser two-photon polymerization technology. The relationship between the FSFP spectral output and the applied force was established, and its microforce sensitivity was obtained to be 2.81 nm/μN, a minimal detectable force is 7.1 nN. The achieved overall measurement range of the device is 69 μN. The adhesion force of MCF-7 breast cancer cells was measured under physiological conditions by using the FSFP. Compared to polymer substrates, the average adhesion force of cells was greater on glass substrates with greater stiffness. The average cell adhesion force value decreased by more than two times after trypsin stimulation. In addition, experiments have shown that cells tend to spread into shuttle shapes on glass substrates with greater stiffness and have a denser actin filaments distribution. To the best of our knowledge, this is the first report on the accurate measurement of the single-cell adhesion force using a miniature all-fiber microforce sensor, which is flexible, fast, and label-free, opening new avenues for single-cell analysis.