Laterally Mobile Ligands: Cellular Response to Dynamic Surfaces

横向移动配体：细胞对动态表面的响应

• 批准号: 7487230
• 负责人: Julie Champion
• 金额: $ 4.48万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-16 至 2010-03-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7487230
• 关键词: Adhesions; Affect; Affinity; Bacteria; Binding; Biocompatible Materials; Biomaterials Research; Cell Adhesion; Cell Communication; Cell Surface Receptors; Cell physiology; Cell surface; Cells; Chemicals; Chinese Hamster Ovary Cell; Diffusion; Engineering; Evaluation; Exhibits; Fluorescence; Goals; In Vitro; Individual; Integrin Binding; Integrins; Label; Lateral; Length; Ligands; Link; Lipid Bilayers; Measures; Mechanics; Membrane; Motion; Movement; Numbers; Peptides; Process; Property; Proteins; Public Health; RGD (sequence); Rate; Recovery; Research; Site; Solid; Structure; Supporting Cell; Surface; System; Tertiary Protein Structure; Testing; Therapeutic; Tissue Engineering; Tissues; Video Microscopy; Walking; Work; base; cell behavior; cell growth; cell motility; design; migration; novel; prevent; protein function; receptor; response; scaffold; single molecule; tool

DESCRIPTION (provided by applicant): The objective of this research is to engineer laterally mobile surface ligands that not only confer control over cell behavior but also allow cells to actively reorganize the surface with which they are interacting. Presentation of ligands on biomaterial surfaces is essential for cell adhesion and function. The manner in which ligands are presented significantly affects these processes, thereby motivating this work. The first aim is to create a ligand-surface pair that allows controlled, lateral ligand migration based on chemical recognition. This will be achieved by designing modular ligands, produced in bacteria, that contain a cell interaction domain and multiple surface binding domains. The cell interaction domain is a known binding peptide to an integrin receptor on the cell surface. The surface binding domains are peptides that bind surface anchor proteins. Independent surface attachment and detachment of multiple surface binding domains will result in lateral migration, or "walking", without the entire ligand losing contact with the surface. The second aim is to determine the effect of ligand structure on mobility. We hypothesize that features such as domain order and spacing, number and affinity of surface binding domains, and peptide display scaffolds will dictate ligand mobility. The third aim is to use this system to study cell behavior on the surface and the ability of cells to manipulate mobile ligands. Characterization of traditional cell responses to biosurfaces, adhesion, spreading, and motility, will reveal any new control over cell behavior due to mobile ligands. However, unlike traditional surfaces, cells on the mobile ligand surface will have the opportunity to actively organize or manipulate surface ligands. Tracking the ligands and corresponding cell surface receptors will provide evidence of this type of interaction. PUBLIC HEALTH RELEVANCE: The relevance of this work to public health lies in fabrication of biomaterials that control cell behavior for therapeutic or tissue engineering applications. Surfaces displaying laterally mobile ligands are a new type of biosurface that not only support cells but also promote unique interactions between cells and surfaces.

描述(申请人提供)：这项研究的目标是设计横向可移动的表面配体，不仅可以控制细胞的行为，还可以让细胞主动重组与其相互作用的表面。配体在生物材料表面的呈现对细胞的黏附和功能至关重要。配体的呈现方式对这些过程有很大影响，从而推动了这项工作。第一个目标是创造一种配体-表面对，允许在化学识别的基础上进行受控的横向配体迁移。这将通过设计在细菌中产生的包含一个细胞相互作用结构域和多个表面结合结构域的模块配体来实现。细胞相互作用结构域是一种已知的与细胞表面整合素受体结合的多肽。表面结合结构域是与表面锚定蛋白结合的多肽。多个表面结合域的独立表面附着和分离将导致侧向迁移，或“行走”，而不会使整个配体与表面失去联系。第二个目标是确定配体结构对迁移率的影响。我们假设，结构域的顺序和间距、表面结合结构域的数量和亲和力以及多肽展示支架等特征将决定配体的流动性。第三个目标是使用这个系统来研究细胞表面的行为和细胞操纵移动配体的能力。对传统细胞对生物表面的反应、黏附、扩散和运动的表征，将揭示由于移动配体对细胞行为的任何新的控制。然而，与传统表面不同的是，移动配体表面上的细胞将有机会主动组织或操纵表面配体。追踪配体和相应的细胞表面受体将为这种类型的相互作用提供证据。公共卫生相关性：这项工作与公共健康的相关性在于制造用于治疗或组织工程应用的控制细胞行为的生物材料。显示横向可移动配体的表面是一种新型的生物表面，它不仅支持细胞，而且促进细胞与表面之间独特的相互作用。