Mutable mechanics in biomaterials : a study of trichocyte keratin and Nvjp-1 protein
Author(s)
Chou, Chia-Ching, Ph. D. Massachusetts Institute of Technology![Thumbnail](/bitstream/handle/1721.1/99614/925533784-MIT.pdf.jpg?sequence=3&isAllowed=y)
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Massachusetts Institute of Technology. Department of Civil and Environmental Engineering.
Advisor
Markus J. Buehler.
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Disulfide bonds and metal-coordination bonds serve as flexible connections on account of their variable bond strengths in different chemical environments. Both bonds can act as an effective switch to stabilize or weaken a protein's geometry. These mechanisms are responsible for protein mutability, enabling distinct biological functions. Understanding the bonds' chemistry and mechanics is important for our knowledge of molecular, cellular and tissue level properties of biological materials that contain high ratios of disulfide bonds or metal-coordination bonds, such as hair and Nereis jaws. In this thesis, we develop the first multiscale framework to study the hierarchical structure of trichocyte keratin proteins with disulfide bonds from a bottom-up approach. We build the first full atomistic structure of keratin k35/k85 heterodimer and upscale to the keratin macrofibril level. Using molecular dynamics simulations, we provide insights into the rupture mechanisms of disulfide bonds in keratin protein and illustrate the importance of the redox environment which governs the rupture mechanisms and locations. Disulfide bonds result in a higher strength and toughness of keratin proteins, but the system loses helical structures under loading, suggesting that disulfide bonds play a significant role in achieving the characteristic mechanical properties of trichocyte keratin. In keratin macrofibrils, disulfide crosslinks contribute to the initial modulus and enhance the robustness of macrofibrils by facilitating cooperative deformation of microfibrils at larger deformation. We also study the mutability of Nvjp- 1 protein with metal-coordination bonds in varied chemical environments from the single molecule level to larger length scales (~[mu]m). Nvjp-1 forms a more compact structure in the presence of Zn ions with more stable intramolecular metal coordination complexes at higher ion concentrations. As pH increases, deprotonation of histidine amino acids weakens the electrostatic repulsion, allowing a greater intramolecular interaction and a shift to a folded conformation. We find that pH also controls the stiffness and modulus of Nvjp-1. This study suggests that the metalcoordination crosslinks and pH induce significant Nvjp-1 aggregation and achieve the contraction of the Nvjp-l stripe observed in experiments. The methodology illustrated here elucidates the trigger mechanism of material mutability for the design of biomaterials with varied properties through a bottom-up computational approach.
Description
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Civil and Environmental Engineering, 2015. Cataloged from PDF version of thesis. Includes bibliographical references (pages 131-146).
Date issued
2015Department
Massachusetts Institute of Technology. Department of Civil and Environmental EngineeringPublisher
Massachusetts Institute of Technology
Keywords
Civil and Environmental Engineering.