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Structure-Activity Relationship of Hydroxyapatite-binding Peptides for Biomimetic Mineralization

Ling, Chen
http://rave.ohiolink.edu/etdc/view?acc_num=akron1461849773

Abstract Details

, Master of Science, University of Akron, Polymer Science.
The formation of mineralized tissues is a highly coordinated, temporally- and spatially-controlled process, and it can be regulated by the interactions between biomolecules with calcium and phosphate ions in solution and with hydroxyapatite (HAP, ideal stoichiometry Ca10(PO4)6(OH)2) crystals. Elucidating the structure-activity relationships between biomolecules and HAP is essential to understanding bone mineralization mechanisms and to developing HAP-based implants as well as designing drug-delivery vectors. Non-collagenous proteins, which exist in bone extracellular matrix, have been suggested to mediate the nucleation and growth of HAP. Furthermore, synthetic HAP-binding peptides, which also present high affinity to HAP surfaces, are believed to perform as alternatives to biomolecules in affecting HAP mineralization. In this study, four peptides (VTK, VTK_s, VTK_7E and pVTK) were selected as model hydroxyapatite-binding peptides (HBPs) to examine the effects of primary amino acid sequence, phosphorylation of serine, presence of charged amino acid residues and net charge of the peptide on secondary conformations and binding affinities in the solution- and bound-states. Binding affinities were determined by conducting mass depletion experiments and fitting the data to adsorption isotherms and the conformations of the peptides in solution- and bound-state were observed by circular dichroism (CD). Results showed that the number of negatively charged residues primarily controlled binding affinity, with little dependence of the other HBP features. Binding affinities increased as VTK ~ VTK_s < VTK_7E < pVTK. The binding affinity and conformation results were in good agreement with our previous MD simulation results thus providing an excellent benchmark for the simluations. Transmission electron microscopy was used in preliminary studies to explore the effect of these peptides on HAP nucleation and growth. Results qualitatively indicated that HBPs may inhibit nucleation of Ca-P nanoparticles and phase transition to crystalline HAP, as well as control crystal growth rates in specific crystallographic directions thus changing the classical needle-like morphology of inorganically-grown HAP crystals to a plate-like morphology. The more strongly binding peptide, VTK_7E, appeared to have a greater effect on all stages compared to VTK and VTK_s. The structure-activity relationships of HBPs revealed from this study provide important insights into the mechanisms of biomineralization and also a theoretical basis for the design of HAP-based materials as well as drug-delivery vectors for bone tissue engineering.
Nita Sahai (Advisor)
William Landis (Committee Member)
121 p.
Polymers

Recommended Citations

Citations

  • Ling, C. (2016). Structure-Activity Relationship of Hydroxyapatite-binding Peptides for Biomimetic Mineralization [Master's thesis, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1461849773

    APA Style (7th edition)

  • Ling, Chen. Structure-Activity Relationship of Hydroxyapatite-binding Peptides for Biomimetic Mineralization. 2016. University of Akron, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1461849773.

    MLA Style (8th edition)

  • Ling, Chen. "Structure-Activity Relationship of Hydroxyapatite-binding Peptides for Biomimetic Mineralization." Master's thesis, University of Akron, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=akron1461849773

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Akron and OhioLINK.