Multiscale Mechanisms of Force Transfer in Tendon

Washington University, Saint Louis MO

Investigators

Abstract

Tendons are soft tissues that connect between muscles and bones to serve two key functions for joints: provide mechanical stability and enable seamless mobility. Tendon injuries are very common and are difficult to treat successfully, in part because of the limited understanding of how mechanical loads transfer through the structures within tendons. Forces applied at the large-scale are transmitted down to the level of cells, which changes the tendon responds biologically. Unfortunately, it remains unclear which components within the complex tendon structure are responsible for force transfer. At the smallest level a tendon has long collagen molecules connected together by other molecule one group of which is flexible and another that is quite stiff. The relative amount of stiff and flexible connections between the collagen molecules determines how strong and stiff the tendon is. However, how the two types of molecular linkages interact to make the tendon strong and stiff mechanically is not properly understood. This gap in knowledge has made it difficult to completely determine how healthy tendons function and how their force-transmission capabilities change after injury. The project will measure the properties of tendons with different amounts of the two linker types and create a model of the tendon built up from the molecular level in order to understand how it functions mechanically at a very basic level. The better model for the tendon has the potential to benefit society by reducing pain, disability, and healthcare costs associated with tendon injuries. This research project includes a number of educational goals. Among them is to build an interactive class section on how mechanics is important in understanding biological materials for a K-12 audience to attract students into STEM fields. Another is to improve a graduate biomechanics course using fundamental concepts of multi-scale mechanics such as are used in this research project. The advanced material in that improved course will train the next generation of scientists needed to continue research in the area. The objective of this project is to determine the role of two specific linking components in tendon mechanics: enzymatic collagen crosslinks and elastic fibers. These tissue constituents are important for mechanical load carriage in tendon, however how they change mechanical properties is not understood in a detailed way. This project will use a combined experimental and computational approach to determine the multiscale mechanical role of these linking components in tendon. Animal models of altered collagen crosslinks and impaired elastic fiber assemblies will be evaluated using biomechanical testing combined with two-photon microscopy and polarized light imaging. Experiments will be complemented with a collagen network computational model to determine individual and coupled mechanical effects of linking components, and evaluate hypotheses on force transmission across length scales. This study will greatly improve understanding of: (1) fundamental tendon mechanics, including the role of linking components across structural levels; (2) effects of complementary or coupled interactions between linking elements; (3) how altered quantities/types of linking components lead to impaired mechanical function; and (4) potential therapeutic applications of controlled modifications to linking components to prevent tissue damage or injury progression. The experimental approach and computational framework provide an excellent system to study fundamental relations that extends to other soft tissues. These concepts could also motivate new ideas in material design and inspire new ways to think about force transfer and assembly of multiscale materials.