Thermodynamic Investigation of Biomacromolecular Interactions

• Author / Creator

  Kabiri, Maryam

• The spontaneous assembly of polypeptides through non-covalent interactions at physiological conditions is the main focus of the presented work and will be discussed from two different perspectives: (i) the interaction of peptide chains with themselves leading to formation of higher order structures (self-assembling peptides); (ii) the interaction of polypeptides with nano-sized surfaces (protein-nanoparticle interactions). Although self-assembling peptides are an important growing class of biomaterials, most of the works in this field have focused upon their various biomedical applications without highlighting the molecular mechanisms which result in their self-assembly into supra-molecular structures inside the body. Herein, through an in-depth thermodynamic analysis utilizing Isothermal Titration Calorimtry technique, the driving forces for self-assembly of ionic self-complementary peptide RADA4 and its variants were identified implying great contribution of molecular hydration and charge to the self-assembly process. Furthermore, the interfacial molecules involved in self-assembly of these molecules was experimentally quantified. It was found that appending five serine residues to C-terminus of RADA4 can overshadow the hydrophobic contribution of RADA segment leading to hydrogen bonding being the main driving force for self-assembly; while presence of 5 lysine residues inhibited RADA4 self-assembly. Secondly, the interaction of proteins with zwitterionic-modified nanoparticles (NPs) was investigated. Although widely studied, the underlying mechanism for the protein-repellent behavior of zwitterionic polymers is largely unknown. A set of thermodynamic investigations was performed to study the interaction of two model proteins (with distinctly different adsorption behaviour) with the surface of zwitterionic-modified silica nanoparticles. The nature of the interaction between proteins and polymer-modified nanoparticle was identified along with highlighting the main driving forces leading to their adsorption onto the nanoparticle’s surface. Moreover, the impact of zwitterion’s spacer length and end-group chemistry on thermodynamics of protein adsorption was analyzed. Overall, our results indicated that the main advantage of zwitterionic polymer modification of surfaces are: i) an increase in water molecules at the interface, ii) lack of counter-ion release from surfaces and iii) lower structural reorganization of the system upon protein-surface interaction. The findings presented in this work will fundamentally impact our understanding of nano-bio interfaces leading to development of more optimum nano-biomaterials in future.

• Subjects / Keywords

  • Thermodynamics
  • Peptide Self-Assembly
  • Isothermal Titration Calorimetry
  • Macromolecular Interactions
  • Zwitterionic Polymers
  • Protein Adsorption

• Graduation date

  Spring 2014

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3FN1110P

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.