Isolated Collagen Mimetic Peptide Assemblies Have Stable Triple-Helix Structures

Area of Science:

• Biochemistry and structural biology
• Biomaterials science
• Chemical physics

Background:

• The high stability of collagen's triple-helix structure is a long-standing question.
• Collagen mimetic peptides (CMPs) are studied as models for collagen and biomaterials.
• Proline hydroxylation enhances collagen stability, with debated roles for stereoelectronic effects versus water interactions.

Purpose of the Study:

• To investigate the structural and stability properties of CMP assemblies in the gas phase, free from solvent influence.
• To differentiate the contributions of stereoelectronic effects and water molecules to CMP stability.
• To explore the potential of gas-phase studies for understanding early collagen fibril formation.

Main Methods:

• Utilized tandem ion mobility spectrometry coupled with mass spectrometry.
• Analyzed CMP assemblies in the gas phase to remove solvent effects.
• Controlled stoichiometry of small triple helix assemblies.

Main Results:

• CMP assemblies maintained their triple-helix structure and stability in the gas phase.
• Results support the significant role of intra-helix stereoelectronic effects in stabilizing the collagen triple helix.
• Demonstrated the feasibility of studying small, stoichiometrically defined triple helix assemblies in the gas phase.

Conclusions:

• Stereoelectronic effects play a crucial role in the inherent stability of collagen triple helices, independent of water mediation.
• Gas-phase studies offer a novel approach to dissecting molecular interactions and early assembly processes in collagen.
• This work provides new insights into the fundamental principles governing collagen structure and the initial stages of fiber formation.