To provide methods and tools for mechanistic understanding of the mechanical behavior of biological tissues, to apply this knowledge for uncovering changes due to ageing and disease, and, to exploit this knowledge for diagnostic and therapeutic use for patients at need.
Multi-scale tissue biomechanics
Tissues are by nature multi-scale hierarchical composite materials made from nanoscale building blocks. The underlying reason for the size of these fundamental building blocks arises from the limited ability of biological cells to assemble large monolithic structures. Therefore, the strategy of living systems for provision of macroscale systems such as the human body is to use hierarchical structures. Within these structures the smallest, nanoscale building blocks are composed to form increasingly larger structural elements that finally lead to whole organs and in combination to a complete living system. This highly smart manner of creating giants from dwarfs has, however, intricate consequences for the biomechanics of living systems and the tissues they contain.
Firstly, the definition of material properties, commonly used in material science to define mechanical properties at the material level in a continuum sense becomes a complicated task. Tissues per se behave according to the structures they contain, and, in many cases, it is impossible to define a representative volume element (RVE), As an RVE needs to be much smaller than the structure of interest and much larger than the next smaller structural element.
Secondly, any alteration of mechanical behavior at the macroscale, due to age or disease could principally manifest itself at any scale within the hierarchical structure of the tissue. Therefore, the analysis of what has changed becomes a true challenge, and warrants a multiscale mechanical assessment. As this is generally impossible, the remaining feasible approach is to take an educated guess as to the level of hierarchy, where the changes are expected to be occurring, and to perform experiments at this level.
Within the experimental biomechanics group we follow this approach to investigate the mechanisms by which the mechanical behavior of healthy biological tissues is specified and by which changes may occur due to aging and disease. Due to the fact that cells can only “build” rather small objects, this approach also necessitates the abilities to prepare and characterize small samples, that is on the micro- and nanoscale. For such purposes, miniature testing systems and custom approaches have been and are constantly developed to provide mechanistic understanding of tissue biomechanics. Research in this area is focused on changes in the mechanical properties of hard- (bone) and soft tissues as a function of age and pathology.
Collagen and Mechanobiology
Additionally, living biological tissues are highly dynamic in nature. Cells contained within the tissues can act as mechanosensors and respond to their mechanical environment via altering tissue composition through protein expression and posttranslational modifications. While such mechanisms are highly important for tissues to adapt to different loading scenarios, they can also lead to pathology, increasing deterioration of mechanical properties of tissues, e.g. after injury or due to overloading. In such situations cells contained within tissues may attempt to provide homeostasis, e.g. to reduce strains experienced the may attempt to express proteins and enzymes to provide locally stiffer tissues. The common building block of all tissues providing mechanical function are collagens, which make up about 25% of all protein mass in the human body. Collagens assemble into collagen fibrils, which are nanoscale fibres and can be considered as the ropes the cells are “hanging” in.
Therefore, collagen fibril mechanics are thought to have large influence on cell behavior, i.e. phenotype and protein expression. Furthermore, cells seemingly have the ability to change the mechanics of their collagen-rich surroundings. It is, however, largely unknown how cells can tune collagen fibril mechanics through post-translational modifications as well as expression of enzymes, which can crosslink the tropocollagen molecules that make up the collagen fibrils.
For this reason our research in this area is largely focused to provide a better understanding how collagen fibril mechanics can be tuned and how effective different tuning parameters are. This necessitates the ability to mechanically characterize collectives of collagen fibrils (such as biopsies) as well as individual collagen fibrils, which we have developed over a course of the last decade. Predominantly atomic force microscopy is employed as a method of choice in this context, as well as custom built instruments for the manipulation and mechanical testing of individual collagen fibrils.