Sequence Specific Liquid Crystallinity in Thick Films of Model Collagen-like Polyhexapeptides

Abstract

To study hierarchical self-assembly of fibrous proteins, methods need to be developed to elucidate the nature of information flow between different levels of structure. The collagens present an interesting example. Sequence-dependent conformational effects are well-known in the collagen triple helix, forming a repetitive sequence (Gly-X-Y; X or Y often hydroxyproline or proline). It should thus be possible to "travel up" the structural hierarchy, and examine the features of long-range ordered structure in light of what is known about sequence and conformational relationships. The next step along this path of structural complexity is an examination of the packing of the collagen triple helices in a condensed phase and the corresponding effect of this organization on any larger domains formed. Studies of crystal structures and solid free surfaces formed by collagen peptides, slowly dried to form glassy solids with very small embedded crystallites, have been used to compare the molecular scale packing behavior of the triple helices within the longer length scale structure of the solid phase. In this instance the peptides go through a state where they are very concentrated viscous, syrupy liquids and where they form solid cholesteric-analogue phases as they dry. A qualitative correlation between the molecular packing geometry of the triple helix and the apparent chirality of the dried cholesteric phase is observed.

Collagen structural hierarchy and susceptibility to degradation by ultraviolet radiation

“…5 shows topographic and phase images of native and heat-denatured collagen films before treatment with UV radiation. The topographic images provide information on the distance between the scanner and each lateral data point of a sample, while the phase images distinguish between domains with different surface properties [28]. Differences in phase indicate differences in material properties between irradiated vs. native collagen films [29].…”

Role of Polyalanine Domains in β‐Sheet Formation in Spider Silk Block Copolymers

“…[31] Collagen is the most abundant extracellular matrix protein and, thus its triple helix has been well studied in great detail. [38][39][40][41] Finally, b-sheet structures found in silks and amyloid proteins also have repetitive motifs. [5,42] Natural occurring silk consists of b-sheet crystalline segments that alternate with amorphous segments.…”

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

“…We have previously documented that these endblocks do not interfere with self-assembly, mesophase formation or structural features. [5,6] …”

“…[3,4] Our lab has also reported evidence for such mesophases in vitro, generated with high concentration collagen-like model peptides to mimic native collagen assembly paths and structural states in vivo. [5,6] The collagen that constitutes the organic matrix of bone is primarily type I. One current model for the assembly and structural organization of type I collagen describes collagen molecules arranged in cholesteric liquid crystals, like the overlying twisted sheets in plywood.…”

“…[20] However, collagen-like peptides with glycine substituted by other amino acids have not been used to study how the effect of the local amino acid substitution can be amplified and affect the long range structure of collagen fibrils. Based on our previous studies on collagen-like peptide liquid crystallinity in vitro [5,6] and extensive studies with native collagen, [21] we hypothesized that type I collagen, during hierarchical assembly, forms liquid crystal mesophases before becoming fixed during fibrillogenesis. Furthermore, extensive evidence from electron microscopy studies of bone tissue sections related to the description of solid state helicoids are reminiscent of cholesteric patterns observed during mesogen assembly in the packing of liquid crystals, albeit the collagen peptides are in the solid state.…”