The mechanics of biomaterials studied at micro- and nano-scales

Abstract

The past few decades have seen the advent of a number of key nanomechanical techniques and instruments being developed and successfully applied to study biomaterials, including optical stretching, atomic force microscope nanoindentation, and micro-pipette aspirator. These have enabled the study of biological samples and biomaterials at the micro- and nano- scales. In this research, a set of such techniques, including atomic-force microscopy, nanoindentation, and optical trapping, was applied to investigate a variety of biological cells and proteins at their nano-scale. In the course of the work, key testing protocols were developed whenever necessary, or new phenomena or behaviour were uncovered.

Firstly, the protein-protein interactions between Hepatitis B surface antigen and its antibodies were studied by measuring the binding force between microspheres coated with such proteins using optical tweezers. A protocol for measuring the protein-protein interactions by using optical tweezers was developed and successfully applied.

Secondly, a rate-jump method was developed to yield intrinsic elastic modulus values that are independent of the experimental conditions from soft biological cells. The elastic moduli of an oral cancer cell line UM1 and non-adherent blood cells were investigated by nanoindentation in an atomic force microscope with a flat-ended tip and an optical tweezers system platform, respectively. The rate-jump method was found to be effective in grading the stiffness values of different cell types. By using this method, tongue squamous cell carcinoma(TSCC)cells with higher metastatic potential were found to show a reduction in elastic modulus as compared to TSCC cells with lower metastatic potential; moreover, the decrease in elastic modulus was accompanied by epithelial–mesenchymal transition and cytoskeleton changes, small nucleus size and large N/C ratio. These findings demonstrate a close relationship between cellular elastic modulus and metastasis of TSCC, and that elastic modulus detected by AFM nanoindentation via the rate-jump method can potentially be used to grade the metastatic potential of cancer cells.

Thirdly, the biomechanical properties of normal leukaemia cells and cells treated with various cancer drugs, including phorbol 12-myristate 13-acetate (PMA), all-trans retinoic acid (ATRA), Cytoxan (CTX) and Dexamethasone (DEX), were measured by indentation tests using optical tweezers. It was found that after treatment by ATRA, CTX Thirdly, the biomechanical properties of normal leukaemia cells and cells treated with various cancer drugs, including phorbol 12-myristate 13-acetate (PMA), all-trans retinoic acid (ATRA), Cytoxan (CTX) and Dexamethasone (DEX), were measured by indentation tests using optical tweezers. It was found that after treatment by ATRA, CTX Finally, the effects of vibrations on cell death were investigated by means of optical trapping. Such experiments have shown that mechanically vibrating the nucleus inside a cell in a near-resonance condition can significantly promote necrosis. The findings lay down a new concept for treating leukemia based on the cell-structure dependent resonance response of targeted malignant cells. Applying mechanical vibrations via a sound-transducer to batches of cells in culture media was also shown to lead to similar cell-type specific necrosis. The results here from a scientific basis for exploring drug-free, vibration-based strategies for killing malignant cells in a cell-type specific manner, which may represent a significant breakthrough for leukemia treatment.