Multiscale structural biology in the biomineralization morphospace: Symmetry-breaking patterning of ‘bio-rocks’ (biominerals without proteins are just rocks)
Unlike geologic rocks/gems which are often faceted, biominerals are often rounded by curvature-generating processes. Biomineralization often occurs as a symmetry breaking event in various tissues and structures. Therein, small biomolecules and peptides, and larger fibrous proteins (like collagen and elastin), and also noncollagenous proteins (some intrinsically disordered) collectively regulate mineral phase transitions and guide crystalline mineral growth and form. This process generates complex (and beautiful, to me) biological architectures having defined functions and mechanical properties. While small-molecule and protein inhibitors broadly prevent soft and compliant tissues from mineralizing, release from this inhibition in bone tissue occurs through local cellular expression of enzymes that degrade these inhibitors in a process we call the Stenciling Principle for extracellular matrix mineralization. Mutations in the genes for these mineralization-regulating enzymes result in inhibitor accumulation leading to debilitating and painful skeletal mineralization defects, and losses of mechanical function.
Correlative, multi-scale imaging approaches are now in common use in structural biology studies. However, this is not generally the case for hard mineralized tissues such as bone and cartilage, or eggshell – cases where fibrous matrices are permeated with a mineral phase that renders them difficult to analyze. Mechanical properties of mineralized fibrous biocomposites originate from nanoscale relations of their constituent parts, and which often propagate across hierarchical levels. Our work utilizes multi-scale imaging approaches (including X-ray and electron tomography, particularly FIB-SEM tomography) combined with deep learning-assisted segmentation methods. This allows us to better understand at multiple levels how mineralization develops in association with fibrous extracellular matrices to form biocomposites having diverse properties and functions.
Bio: Marc McKee holds the Canada Research Chair in Biomineralization at McGill University’s Faculty of Dental Medicine and Oral Health Sciences, and the Faculty of Medicine and Health Sciences. He received his Ph.D. degree from McGill University in cell biology, followed by postdoctoral training at Harvard and the Children’s Hospital Boston, and then appointments at the Forsyth Institute in Boston and University of Montreal. McKee’s research focuses on biomineralization in bones, teeth, otoconia and eggshells, and in pathologic ectopic calcification. With over 260 scientific papers, and over 39,000 citations of his research, he has received two Distinguished Scientist Awards from the International Association for Dental Research, the Adele Boskey Esteemed Scientist Award from the American Society for Bone and Mineral Research, the C.P. Leblond Award from the FRQS Quebec Network for Bone and Oral Health Research, and a Lifetime Achievement Award from the Canadian Connective Tissue Society.