Theoretical mathematics, polarized light microscopy and computational models in healthy and pathological bone.

Abstract

The needs of everyday life, such as counting and measuring, are roots of theoretical mathematics. I believe these roots are why mathematical ideas ground research so amazingly well within many scientific fields. Initially trained as a theoretical mathematician and having collaborated with non-mathematicians in the field of bone research, I address the advantages and challenges of collaborations across fields of research among investigators trained in different disciplines. I report on the mathematical ideas that have guided my research on the mechanics of bone tissue. I explain how the mathematical ideas of local vs. global properties influence my research. Polarized light microscopy (PLM) is a tool that I use consistently, in association with other microscopy techniques, to investigate bone in its healthy state and in the presence of bone disease, in humans and in animal models. I review the results that I and investigators around the world have obtained with PLM. Applied to thin bone sections, PLM yields extinct (black) and bright (white) signals that are interpreted in terms of the orientation of collagen type I, by means of other microscopy techniques. Collagen type I is an elementary component of bone tissue. Its orientation is important for the mechanical function of bone. Images obtained by PLM at a specific bone site yield big data sets regarding collagen orientation. Multiple data sets in respect of multiple sites are often needed for research because the bone tissue differs by location in response to the distinct forces acting on it. Mathematics, defined by philosophers as the theory of patterns, offers the backdrop for pattern identification in the big data sets regarding collagen orientation. I also discuss the computational aspect of the research, pursuant to which the patterns identified are incorporated in simulations of mechanical behaviors of bone. These mathematical ideas serve to understand the role of collagen orientation in bone fracture risk.