CAREER: Development of Hierarchical Plant Virus Assemblies for Probing Cell-Matrix Interactions

在美国国家科学基金会有机和高分子化学项目的支持下，南卡罗来纳州大学化学系的王倩教授将专注于开发具有定义模式的病毒颗粒（VP）和修饰VP的分级组装体，并在此类组装体上展示配体以研究细胞反应。PI将带领学生和研究人员团队探索基于纳米或中尺度病毒和病毒缀合物自组装的支架合成，并探测细胞与此类病毒组装体的细胞外相互作用。最终的目标是模仿，从而获得更好地了解哺乳动物细胞外基质（ECM）的复杂性和动态。本研究将使用两种类型的细胞，即NIH-3 T3成纤维细胞和大鼠骨髓基质细胞（rBMSC）。这些是研究基于病毒的支架如何影响细胞粘附、铺展、迁移、增殖、分化和聚集的理想模型系统。该方法依赖于PI在生物偶联化学、受控VP组装和细胞生物学领域产生的初步结果。球形和杆状植物病毒已被成功地组装成单层在两个不混溶液体的界面。发现这些类型的病毒组装体表现出有趣的细胞粘附行为，这激发了进一步开展这方面研究的兴趣。本研究的主要目的是：（1）从基因和化学的角度展示VP外表面的细胞结合基序;（2）研究VP在液-液界面或聚合物表面的二维自组装;（3）表征细胞在二维病毒阵列上的粘附和培养，并研究细胞对VP在二维阵列中排列的反应;（4）研究rBMSC与VP组装体的粘附、增殖和分化;（5）研究细胞粘附和细胞迁移对带有细胞结合基序的病毒组装体的排列模式的响应。王教授将凭借这项CAREER奖在纳米分辨率上探索细胞行为，这将对科学和社会产生重大影响。更好地了解分化，迁移和生长中涉及的细胞机制将提高对纳米级的理解，并将导致技术先进的材料在生物医学（智能植入物，组织工程和再生，自我修复支架和多功能膜）中具有潜在的应用。这种多学科的研究将使学生有机会发展许多先进的研究技能，并提供宝贵的社交网络，这将有助于他们在未来的职业生涯。已经建立了一个生物纳米粒子技术开放实验室（OLBT），作为培训多层次参与者的统一平台-从高中生到本科生和研究生，再到博士后研究员。特别是，PI计划设计一系列与生物纳米技术相关的实用和简单的教育实验，用于教学目的。这些实验可以用于研究生和本科生课程的教学，以及为高中生提供纳米科学实践经验的“生物纳米技术夏令营”。

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.