Hierarchical Assembly of Collagen‐Like Peptides in vitro Provides Structural Causes of Osteogenesis Imperfecta

Abstract

Collagen type I peptides, representative of native to disease states for the bone disease, Osteogenesis imperfecta, were studied with regard to self-assembly into triple helices and liquid crystalline mesophases. The purpose of the study was to establish insight into collagen mutations in terms of propagation of single chain defects up the scale of materials hierarchy, toward solid state fibril assemblies formed from collagen. Studies carried out in vitro demonstrated the value of this approach in establishing in vitro disease models, as the degree of collagen disruption could be recapitulated by the point mutations to show major impact on macroscopic features. Fourier transform infrared spectroscopy, circular dichroism, atomic force microscopy and optical ellipsometry were used to assess the structural and morphological changes at the various length scales post assembly. The results demonstrated that glycine to alanine to aspartic acid single substitutions in the collagen peptides progressively disrupted normal assembly, reflected in lower thermal stability, loss of triple helical structure and loss of mesophase formation. This approach can provide a basis upon which to study collagen biomaterial templates for controlled hydroxyapatite formation and changes in cell signaling related to bone remodeling, related to the severity of the disease.

Does l to d-amino acid substitution trigger helix → sheet conformations in collagen like peptides adsorbed to surfaces?

“…In addition, the peak at about 1685 cm −1 suggests the occurrence of turns in the secondary structure of the peptides. Further, the bands were observed in the region of 1618-1623 cm −1 , which confirms the presence of intermolecular aggregates [64][65][66]. The FT-IR analysis results corroborate with the circular dichroic secondary structural analysis.…”

Dynamic and Reversible Polymorphism of Self-Assembled Lyotropic Liquid Crystalline Systems Derived from Cyclic Bis(ethynylhelicene) Oligomers

“…It is indicated that judicious molecular design can be used to control the morphology of self-assembly and the alignment of the resulting fibers. It should also be noted that the LLC formation by self-assembly of synthetic double-helix-forming molecules − ,, has not been previously reported, and the results are reminiscent of the property of biological double-helical molecules and polymers such as DNA and RNA, polysaccharides, and actin , that form LLCs in aqueous media.…”

“…This is in contrast to acyclic systems, for example, ( M )-D- 4 /( P )-D- 5 , which forms gels composed of randomly oriented fibers. This is a notable LLC formed by the self-assembly of synthetic double helix organic molecules. , (2) The self-assembled system showed dynamic and reversible polymorphism between two ordered structures, the LLC and a turbid gel composed of randomly oriented bundles, attributed to a temperature change in a closed system (Figure d,e). The results are reminiscent of the self-assembly property and the dynamic and reversible polymorphism of actin, which play important roles in biological systems.…”