(7n) Creation of Self-Assembled Materials from Recombinant Fusion Proteins for Advanced Biomedical Platforms

My research interests are to combine characterization of soft matter self-assembly, with recombinant protein materials fabrication, and biofunctional assessment of self-assembled materials for advanced biomedical platforms.

Self-assembly of biomolecules has been harnessed to create novel supramolecular architectures at the nanometer to micrometer scale with high complexity. Among different types of biological building blocks, proteins are potent molecules that can be used for many applications such as therapeutics, sensors, and biocatalysts due to their specific bioactivity based on amino acid sequences and folded structures. Furthermore, the protein self-assembled biomaterials enable us not only to overcome the limitations of soluble proteins such as stability, localization, and recovery but also to enhance their functions with engineered supramolecular structures. The biggest advantage of using proteins as self-assembling building blocks is that the protein domains can be designed to confer specific functions to engineered biomaterials via recombinant technology. Fusion of either a functional protein or an assembly domain to a leucine zipper domain makes the materials design strategy modular, based on the high affinity of the zippers.¹

To establish a rational strategy to create self-assembled materials from recombinant proteins with tunable structure and size, understanding of their phase behavior as a function of diverse physical parameters including concentration, temperature, buffer pH and ionic strength is critical. Yet, basic assembly principles of recombinant fusion proteins are underdeveloped due to the greater complexity of protein-protein interactions than other molecules. The first goal of my research is to investigate recombinant protein self-assembly behavior in terms of structure and physical property under different environment conditions by using x-ray/neutron scattering, dynamic light scattering, microscopy techniques and quartz crystal microbalance with dissipation energy monitoring (QCM-D). During my Ph.D. program, I have been training in neutron scattering for structural characterization of the macromolecular self-assembled platforms at the nm-scale, along with physical property characterization using QCM-D and AFM.^2-4

Ultimate goals of my research are to identify fundamental structural knowledge of the self-assembly of recombinant fusion proteins and to use this information to create innovative protein-assembled materials from specifically designed, bioactive globular proteins. For example, functional globular protein-incorporated vesicles can be utilized for drug delivery vehicles, micro-reactors, or bio-sensors, and nanosheets or hydrogel platforms can be developed for wound healing patches or stem cell scaffolds. I believe that self-assembled materials from specifically designed recombinant proteins will create a number of advanced biomedical applications since the biological functions and stimuli-responsiveness can be inserted into the platforms by protein materials design via recombinant technology. Beyond the fabrication of new biomaterials, the fundamental studies on protein self-assembly into higher ordered structures will also give scientific inspiration to other soft matter research fields.

Teaching Interests:

During my career development, I was fortunate enough to have served as a teaching assistant at “Quantum Mechanics” at Seoul National University, and lecturer for an intermediate level course “Interfacial Engineering” at Kyunghee University. I found that my professional experience provided me a broad view that is useful in assisting students with managing projects and assignments. These experiences have built my confidence and an interest in teaching. I can teach the stem courses in Chemical Engineering such as “Physical/Organic Chemistry”, “Chemical Process Principles”, and “Chemical Engineering Thermodynamics”. More specifically, I am confident to teach “Polymer Engineering and Characterization” and “Protein Engineering” for undergraduate students, and current trends in “Interfacial Engineering”, “Soft Matter Self-Assembly Principle and Applications”, and “Scattering Techniques” for graduate students. I look forward to the opportunity to not only teach existing courses but also work to develop new ones that I can contribute to. Aside from teaching courses, I have a lot of experience in mentoring undergraduate and graduate students during my academic carriers. From these experiences, I have learned the PI’s role should be much bigger. I will share my experiences, successes, and struggles with my students to encourage them and create a supportive environment that allows all students to flourish.

Research Experiences:

My academic training during the doctoral program and 3 years of experience working as a postdoctoral researcher prepare me to be an effective researcher and instructor. My doctoral dissertation was conducted in consultation with Prof. Kookheon Char at Seoul National University (School of Chemical and Biological Engineering), under the thesis title of “Functional Multilayer Films with Controlled Nanostructures for in vitro Cell Studies”. I have investigated stimuli-triggered changes in structure and property of polymer thin film multilayers, which are specially designed for biomedical applications such as drug eluted coatings, cancer cell study platforms.^5-7 During my Ph.D. program, I had been able to strengthen the basics in macromolecular self-assembly and an integrated design of polymer-assembled platforms for biological applications. In addition to my dissertation research, other areas that interest me for future research stem from my goal of developing a new class of biomaterials via recombinant technology. First, I have worked on hybrid microbubbles consisting of recombinant proteins and biocompatible triblock copolymers at the University of Pennsylvania with Profs. Daeyeon Lee and Daniel A. Hammer. I have focused on controlling the size and mechanical properties of the recombinant protein microbubbles generated by microfluidic devices for antivascular ultrasound theranostics.⁸ I believe that the experience in using microfluidics, soft lithography to fabricate microbubbles, emulsions, vesicles as well as characterizing the mechanical properties by micropipette aspiration enlarged my research capability in addition to the doctoral background in engineering polymer multilayers. Then, I moved into Georgia Institute of Technology (PI: Julie A. Champion who is an expert in protein engineering) to learn more about the recombinant fusion protein materials. Here, I have designed a new functional fusion protein that can self-assemble into vesicles and engineered the protein vesicles for cancer targeting applications and antibacterial performance. In synergy with my forte on fundamentals of soft matter assembly and postdoctoral experiences in the design of new biomaterials from recombinant proteins, I have been able to develop multipotent self-assembled materials made from the recombinant fusion proteins.

Successful Proposals: The proposal # DMR - 1709428 titled “Protein Vesicles: Understanding Self-Assembly of Fusion Proteins into Vesicles to Engineer Structures and Biofunctional Properties” is being considered for an NSF three-year award at the requested amount of $393,605.

Future Direction:

I am extremely interested in obtaining a faculty position in School of Chemical Engineering, Biomolecular Engineering, and/or Materials Science, where I can contribute to its focus on education and research. I would like to continue my research on creating multipotent self-assembled materials from recombinant proteins and biopolymers and devote to lead campus and professional service activities as a faculty. I am confident that my skills, knowledge and personality are well-aligned with the role.

Selected Publications:

1. Jang, Y.; Champion, J. A., Self-Assembled Materials Made from Functional Recombinant Proteins. Accounts of Chemical Research 2016, 49, 2188-2198.
2. Jang, Y.; Seo, J.; Akgun, B.; Satija, S.; Char, K., Molecular Weight Dependence on the Disintegration of Spin-Assisted Weak Polyelectrolyte Multilayer Films. Macromolecules 2013, 46, 4580-4588.
3. Jang, Y.; Akgun, B.; Kim, H.; Satija, S.; Char, K., Controlled Release from Model Blend Multilayer Films Containing Mixtures of Strong and Weak Polyelectrolytes. Macromolecules 2012, 45, 3542-3549.
4. Son, H.*; Jang, Y.*; Koo, J.; Lee, J.-S.; Theato, P.; Char, K., Penetration and exchange kinetics of primary alkyl amines applied to reactive poly(pentafluorophenyl acrylate) thin films. Polym J 2016, 48, 487-495. (*Equal Contribution)
5. Jang, Y.; Lee, H.; Char, K.; Nam, J.-M., Transparent, Nanoporous, and Transferable Membrane-Based Cell–Cell Paracrine Signaling Assay. Advanced Materials 2015, 27, 1893-1899.
6. Lee, H.*; Jang, Y.*; Seo, J.; Nam, J.-M.; Char, K., Nanoparticle-Functionalized Polymer Platform for Controlling Metastatic Cancer Cell Adhesion, Shape, and Motility. ACS Nano 2011, 5, 5444-5456. (*Equal Contribution)
7. Jang, Y.; Park, S.; Char, K., Functionalization of polymer multilayer thin films for novel biomedical applications. Korean Journal of Chemical Engineering 2011, 28, 1149-1160.
8. Jang, Y.; Jang, W.-S.; Gao, C.; Shim, T. S.; Crocker, J. C.; Hammer, D. A.; Lee, D., Tuning the Mechanical Properties of Recombinant Protein-Stabilized Gas Bubbles Using Triblock Copolymers. Acs Macro Letters 2016, 5, 371-376.