kT-scale Protein & Carbohydrate Interactions on Synthetic Materials & Cell Surfaces

kT级蛋白质

• 批准号: 1402739
• 负责人: Michael Bevan
• 金额: $ 30万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1402739&HistoricalAwards=false
• 关键词: kT; scale; Protein; & Carbohydrate

PI: Bevan, Michael A. Proposal Number: 1402739Institution: Johns Hopkins University Title: kT-scale Protein & Carbohydrate Interactions on Synthetic Materials & Cell Surfaces Many important cellular interactions involve "weak" interactions, which are difficult to characterize by current techniques. The PI proposes to move into new territory, in terms of directly characterizing these weak intermolecular interactions of biomolecules, by using a technique, Diffusing Colloidal Probe Microscopy (DCPM), developed by the PI's group. The proposal will examine two systems of biological importance, which were also chosen for their significance to biomedical problems: stem-cell based tissue engineering and cancer metastasis. Success in the development of the technique for studying weak biological interactions will have an impact on the understanding of such interactions in cell-cell adhesion, cell migration, tissue morphogenesis, metastasis, immunology, and other cellular processes.Weak biomolecular interactions, on the order of kT, play an important role in cell-cell adhesion, cell migration, tissue morphogenesis, metastasis, immunology, and other cellular processes. While there are standard mechanical methods for measuring strong interactions (pN forces), weak interactions are generally measured_ indirectly_ by spectroscopic means. The PI proposes to move into new territory, by directly characterizing these interactions using DCPM, which offers spatial and temporal resolution, statistical significance, and directness not accessible using scanning probes or spectroscopic methods. In essence, DCPM passively monitors Brownian excursions of "diffusing probes" and exploits these natural gauges for time (a2/D), energy (kT), force (fN), and length (nm) when interrogating the interaction of proteins and carbohydrates. This is inherently a nanoscale technique because it harnesses Brownian motion as a useful tool to directly measure kT interactions between proteins rather than avoiding stochastic thermal motion as an undesirable complication of nanoscale systems. Two systems will be studied, CD44-HA interactions and heterophilic cadherin interactions (in the presence of calcium ions) on supported bilayers. The development of DCPM for studying weak biological interactions will have an impact on the understanding of such interactions in cell-cell adhesion, cell migration, tissue morphogenesis, metastasis, immunology, and other cellular processes.

PI：Bevan，Michael A.提案编号：1402739 Institution：Johns Hopkins University标题：KT规模的蛋白质和碳水化合物相互作用在合成材料和细胞表面上的许多重要的细胞相互作用涉及“弱”相互作用，这些相互作用很难通过当前技术表征。 PI提议通过使用技术直接表征生物分子的这些弱分子间相互作用而进入新区域，该技术通过PI组开发了胶体探针显微镜（DCPM）。该提案将检查两个生物学重要性系统，这些系统对生物医学问题的重要性也被选择：基于干细胞的组织工程和癌症转移。在研究弱生物学相互作用技术发展方面的成功将影响对细胞粘附，细胞迁移，组织形态发生，转移，免疫学和其他细胞过程的这种相互作用的理解。对KT的良好生物分子相互作用，对细胞粘附，细胞迁移，环境，并在细胞粘附过程中，对KT的序列起重要作用。尽管有用于测量强相互作用的标准机械方法（PN力），但通常通过光谱均值来测量弱相互作用。 PI建议通过使用DCPM直接表征这些相互作用来进入新区域，DCPM提供了空间和时间分辨率，统计显着性和直接性，无法使用扫描探针或光谱法无法访问。从本质上讲，DCPM被动地监视布朗横文的“扩散探针”，并在询问蛋白质和碳水化合物的相互作用时，将这些天然仪表用于时间（A2/D），能量（KT），力（FN）和长度（NM）。这本质上是一种纳米级技术，因为它可以利用布朗运动作为直接测量蛋白质之间的KT相互作用的有用工具，而不是避免随机热运动作为纳米级系统的不良并发症。将研究两个系统，即CD44-HA相互作用和在钙离子存在的异质钙粘蛋白相互作用（在受支持的双层）上。用于研究弱生物相互作用的DCPM的发展将影响对细胞粘附，细胞迁移，组织形态发生，转移，免疫学和其他细胞过程中这种相互作用的理解。