With the support of this CAREER Award from the Organic and Macromolecular Chemistry Program at the National Science Foundation, Professor Qian Wang of the Department of Chemistry at the University of South Carolina will focus on developing hierarchical assemblies of viral particles (VPs) and modified VPs with defined patterns, and displaying ligands on such assemblies to study cell responses. The PI will lead teams of students and researchers to explore the synthesis of scaffolds based on self-assembly of viruses and viral conjugates at nano- or mesoscale, and to probe the extracellular interactions of cells with such viral assemblies. The ultimate goal is to mimic and thereby gain better understanding of the complexities and dynamics of the mammalian extracellular matrix (ECM). Two types of cells, i.e. NIH-3T3 fibroblasts and rat bone marrow stromal cells (rBMSCs) will be employed in the study. These are ideal model systems to study how the viral based scaffolds will influence the cell adhesion, spreading, migration, proliferation, differentiation and clustering. The approach relies on preliminary results generated by the PI in the areas of bioconjugation chemistry, controlled VP assemblies, and cell biology. Spherical and rod-like plant viruses have been successfully assembled as a monolayer at the interface of two immiscible liquids. It was found that these types of viral assemblies showed interesting cell-adhesion behaviors, which stimulated interests to further pursue this research. Goals of the research are, (1) to display cell binding motifs on the exterior surface of VPs genetically and chemically; (2) to investigate the 2D self-assemblies of VPs at the liquid-liquid interfaces or on polymeric surfaces; (3) to characterize the cell adhesion and cell culture on the 2D viral arrays, and to study the cell response to the arrangement of VPs within the 2D arrays; (4) to study the adhesion, proliferation and differentiation of rBMSC with respect to VP assemblies; and (5) to study the cell adhesion and cell migration in response to the aligning patterns of viral assemblies which bear cell binding motifs.
With this CAREER award Professor Wang will probe cellular behaviors at nanometer resolution that will significantly impact both scientific and social communities. Gaining a better understanding of the cell machinery involved in differentiation, migration and outgrowth will improve understanding at the nanoscale level and will lead to technologically advanced materials with potential applications in biomedicine (intelligent implants, tissue engineering and regeneration, self-healing scaffolds, and multifunctional membranes). This multidisciplinary research will give students a chance to develop many advanced research skills and provide invaluable social networks that will serve them well into their future careers. An Open Laboratory for Bionanoparticle Technology (OLBT) has been established to serve as the unifying platform for the training of multilevel participants - from high school students, to undergraduate and graduate students, and to postdoctoral fellows. In particular, the PI plans to design a series of practical and simple educational experiments related to bionanotechnology for the purpose of teaching. Such experiments can be used in the teaching of graduate and undergraduate courses, as well as in the 'Summer Camp for Bionanotechnology' for high school students that will provide hands-on experience in the nanosciences.
This research focuses on developing hierarchical assemblies of viral particles (VPs) and modified VPs with defined patterns, and displaying ligands on such assemblies to study cell responses. The PI lead teams of students and researchers to explore the synthesis of scaffolds based on self-assembly of viruses and viral conjugates at nano- or mesoscale, and to probe the extracellular interactions of cells with such viral assemblies. Our ultimate goal is to mimic and thereby gain better understanding of the complexities and dynamics of the mammalian extracellular matrix (ECM). Here is a list of the significant achievements: (1) Versatile methods have been developed to modify the surface properties of viral particles. (2) Novel assembly methods have been developed for the two-dimensional assembly of bionanoparticles at the interface of aqueous and oil layers. (3) A facile strategy has been developed for the assembly of functional proteins and protein particles to form core-shell nanoparticles. (4) Anisotropic particles and functional proteins to get organized into 3D structures by convective assembly or flow assemblies. (5) Using bionanoparticle (surface functionalities and nanotopography) to modulate the cellular response (alignment, migration and differentiation). In particular, we found that the surface topography can play a major role to modulate the differentiation of mesenchymal stem cells. (6) With the support of the NSF award, we have successfully achieved (if not exceeded) all our goals. The results have been disseminated as more than 30 publications in peer reviewed journals. The PI has delivered more than 50 invited talks in conferences, workshops, and universities. (7) In the whole entire period of the grant, a great numbers of graduate students, undergraduate students, postdoctoral fellows and high school students have been trained/involved in this multidisciplinary research project. (8) We filed three patents and established a start-up company partially based on the technology developed in this project. (9) We have established multidisciplinary collaborations with scientists in different research institutes and National labs. (9) The PI has created an Open Laboratory for Bionanoparticle Technology (OLBT) at USC, in alliance with The Scripps Research Institute. The initiative of OLBT is to offer a platform for the research and educational activities related to bionanoparticle technology. The OLBT creates a unique multidisciplinary research platform for collaborative research as well as students training. In addition, OLBT offers a laboratory space for the other educational or outreach initiatives, including the USC regular courses EMCH-792k "Nanomaterials: Synthesis, Characterization and Applications", ENVR-350X "Introduction to nanoscience", and STEM 101 "Concepts and Connections in Science, Technology, Engineering and Math", USC Citizen School for Nanoscience, Girl Scouts "Exploration in Science", and the "Adventure Summer Camp for Bionanotechnology".
