Research

We are a group of chemists who use physical measurement methods to study the behavior of biomacromolecules.

Project 1: Dilution induced complex coacervation in polyelectrolyte–micelle and polyelectrolyte–protein systems

Complex coacervation is a form of liquid-liquid phase separation (LLPS) resulting from strongly associative interactions among oppositely charged macromolecules. The dense liquid phase enriched in the macromolecules is the coacervate phase. Due to their peculiar yet interesting properties such as extremely low surface tension and stimuli-responsive, complex coacervates have been used in tissue engineering, delivery systems, and recently, the research into protocells. In addition to charge-related parameters such as pH, ionic strength, and stoichiometry between oppositely charged macromolecules, complex coacervation can also be induced by simply adjusting the total macromolecular concentration (CT). If CT of a system is above the critical value, complex coacervation is suppressed, and the macromolecules are crowded in a single phase. As CT is decreased below the critical value upon iso-ionic dilution, complex coacervation will occur, and this process is known as the Dilution-Induced Complex Coacervation (DICC). Although DICC has been used as delivery platforms in personal care products, knowledge on the detailed molecular mechanism underlying such a phase separation event is still lacking. The proposed research will characterize various intra- and inter-molecular interactions and the structural transition of macromolecular complexes during the course of DICC. Such information will help us discern a common mechanism so that such a phenomenon can be used in other potential applications. In addition to the in-solution studies, the deposition mechanism as well as the microstructure of the deposited complex coacervate layer onto various surfaces, will also be investigated in this study.

 

Project 2: Exploring the impacts of protein charge anisotropy on the short-term and long-term colloidal stability and viscosity of biopharmaceutical formulations

Biopharmaceuticals, mostly therapeutic proteins, represent a major class of medicine nowadays for the treatment of a wide range of medical conditions, including cancer, infections, auto-immune diseases, and metabolic disorder. Due to limitations on injection volume via subcutaneous administration, protein therapeutics need to be formulated at high concentrations in order to achieve the desired therapeutic dosage. At high protein concentrations, the spatial distances between individual protein molecules decrease significantly. As a result, a variety of non-specific protein-protein interactions (PPI) will occur, leading to the reduced colloidal stability and elevated solution viscosity that will compromise the quality and safety of the products. Therefore, therapeutic proteins require special formulations to ensure the long-term colloidal stability and desired viscosity profile of the final products.  This project will investigate the relationships among the protein charge anisotropy, non-specific PPI, and the viscosity behavior of concentrated protein formulations. The proposed research will provide solid experimental and theoretical foundations for more efficient formulation development.

 

Project 3: Elucidating the mechanism of actoin of aluminum-based adjuvants

The development of a vaccine product not only requires the selection of suitable antigens that can elicit specific immune responses toward the targeted pathogen, but also involves the development of adjuvants to promote the innate immune response. Among others, aluminum-based adjuvants are most widely used to formulate vaccine products due to their excellent safety and efficacy records. This project aims to characterize interactions between aluminum adjuvants with biological macromolecules, including antigen proteins and lipid membranes. The interaction between aluminum adjuvants and biomacromolecules represents the first step toward an activated signaling pathway. Thus such knowledge is of fundamental importance towards a comprehensive understanding of the adjuvanticity of aluminum salts.

 

We are constantly looking for talented and motivated students to join our group. Interested graduate and undergraduate students are welcome to contact Dr. Xu at amyxu@lsu.edu for more information on available projects :)