Biomechanics at the multiscale: From tissues to subcellular compartments

The mechanical properties of biological materials and biomaterials are fundamental to the correct functionality of living organisms. Nowadays, it is recognized that several biological processes are driven by mechanical stimuli. Biomechanics is a field of science that studies these processes, and it is currently recognized as an important part of biology, complementing the classical view of signal transmission governed by chemical pathways. In this context, it is evident that modifications of the physiological conditions are associated with or can be the cause of pathological states. These modifications act on multi-level that encompasses a wide range of length scales, from the tiniest molecules up to entire organs and back. In this thesis, different biophysical approaches are applied to characterize the mechanical behavior of the biological samples and biomaterials. First, biomechanics and its applications from the subcellular to the tissue level are introduced. Then, the methodologies employed in this research are covered. In particular, Atomic Force Microscopy (AFM) and Brillouin microscopy (BM) are focused, as they are the main techniques that are used in this thesis. Although other techniques with a large diffusion in the study of mechanics of biological samples but not applied in this research are presented in Appendix 1. Chapter 3, is devoted to the main focus of this activity: investigating the mechanical properties of eukaryotic cell nuclei—an intriguing yet unsolved challenge in the field of biology. The capability to obtain affordable and reproducible results is important, particularly in detecting pathological affection in healthy physiological conditions. AFM, as a golden standard method in cell mechanics, is primarily used. Subsequently, the results are correlated with that of the non-contact Brillouin microscopy (BM), which is an emerging technique in biological investigations. The conclusions could suggest an approach for the study of nuclear mechanics, being an important tool in the investigation of pathologies that affect the cell nuclear environments, such as laminopathies. The scale of the study is then expanded to the tissue level in collaboration with Prof. Leonardo Ricotti (Scuola Superiore Sant’Anna, Pisa, Italy). This collaborative research aims to study the mechanical properties of cartilage tissues by inducing degeneration to simulate osteoarthritis conditions. The goal is to provide quantitative results as a source for developing a new tool for quantitative evaluation of pathological state in vivo using Quantitative Ultra-Sound (QUS). This work is presented in Chapter 4. Lastly, in collaboration with the same group, biomaterials of SBS polymer doped with piezoelectric nanoparticles were investigated by AFM. The aim is to use these films for the myogenic differentiation of stem cells by mechanical cues for tissue engineering purposes.