Studies of chain substitution caused sub-fibril level differences in stiffness and ultrastructure of wildtype and oim/oim collagen fibers using multifrequency-AFM and molecular modeling

T Li and SW Chang and N Rodriguez-Florez and MJ Buehler and S Shefelbine and M Dao and KY Zeng, BIOMATERIALS, 107, 15-22 (2016).

DOI: 10.1016/j.biomaterials.2016.08.038

Molecular alteration in type I collagen, i.e., substituting the alpha 2 chain with alpha 1 chain in tropocollagen molecule, can cause osteogenesis imperfecta (01), a brittle bone disease, which can be represented by a mouse model (oim/oim). In this work, we use dual- frequency Atomic Force Microscopy (AFM) and incorporated with molecular modeling to quantify the ultrastructure and stiffness of the individual native collagen fibers from wildtype (+/+) and oim/oim diseased mice humeri. Our work presents direct experimental evidences that the +/+ fibers have highly organized and compact ultrastructure and corresponding ordered stiffness distribution. In contrast, oim/oim fibers have ordered but loosely packed ultrastructure with uncorrelated stiffness distribution, as well as local defects. The molecular model also demonstrates the structural and molecular packing differences between +/+ and oim/oim collagens. The molecular mutation significantly altered sub-fibril structure and mechanical property of collagen fibers. This study can give the new insight for the mechanisms and treatment of the brittle bone disease. (C) 2016 Elsevier Ltd. All rights reserved.

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