Microenvironments Fit for Proteins

适合蛋白质的微环境

• 批准号: 1507739
• 负责人: Deborah Leckband
• 金额: $ 39万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1507739&HistoricalAwards=false
• 关键词: Microenvironments; Fit; Proteins

NonTechnicalThis research program will address the grand challenge of identifying material properties that preserve or even enhance the stability of immobilized protein components in devices or materials. Many biological macromolecules have unique, useful properties that are exploited in applications ranging from biosensors to drug carriers that seek out diseased cells in the body. But these applications typically require incorporating proteins into non biological materials in ways that completely alter the protein environment and often destroy the very properties sought. In this research, the PIs will address the grand challenge of determining how to engineer material properties to preserve (or shut down) these unique protein functions. Results from this research will have broad impact, by uncovering guidelines for how to engineer material microenvironments that are fit for proteins. Because of the widespread use of immobilized bio-macromolecules in industry and in research, the PIs findings will have broad impact across a range of disciplines. Through several outreach activities, the PIs will also expose middle school girls and minority students to this exciting research and the many ways our discoveries can have a positive impact on society.TechnicalTo address the challenge of preserving immobilized protein stability, this program will use two powerful, complimentary experimental approaches. First, molecular force measurements will identify the nanoscale surface properties associated with surface chemistries that determine how materials interact with proteins. Next, the PIs will establish how those nanoscale properties alter protein stability, by using novel temperature-jump measurements to measure the folding rates of immobilized proteins. The use of nanoscale force measurements and temperature-jump measurements at submicron resolution will uniquely identify causal relationships between molecular scale interfacial force fields and the surface chemistries that protect or shut down protein function. This program extends prior investigations of thermally responsive poly(N-isopropylacrylamide) to zwitterionic coatings, which display exceptional protein-resistant properties and apparent protein/bio-compatibility, despite significant differences in composition and architecture. Molecular force measurements and transformative surface-specific temperature-jump measurements will reveal physical chemical coupling between the surface microenvironment and protein folding stability. These studies will bridge the gap between nanoscale surface chemistries and immobilized protein folding stability, and identify transformative new design rules for engineering protein-protective microenvironments.

本研究项目将解决识别材料特性的重大挑战，这些特性可以保持甚至增强固定在设备或材料中的蛋白质成分的稳定性。许多生物大分子具有独特的、有用的特性，被广泛应用于从生物传感器到寻找体内病变细胞的药物载体等领域。但这些应用通常需要将蛋白质以完全改变蛋白质环境的方式结合到非生物材料中，并经常破坏所寻求的特性。在这项研究中，pi将解决如何设计材料特性以保持（或关闭）这些独特的蛋白质功能的重大挑战。这项研究的结果将通过揭示如何设计适合蛋白质的材料微环境的指导方针，产生广泛的影响。由于固定化生物大分子在工业和研究中的广泛应用，PIs的发现将在一系列学科中产生广泛的影响。通过一些外展活动，pi还将向中学女生和少数民族学生展示这项令人兴奋的研究，以及我们的发现可以在许多方面对社会产生积极影响。为了解决保持固定蛋白稳定性的挑战，该计划将使用两种强大的，互补的实验方法。首先，分子力测量将确定与表面化学相关的纳米级表面性质，这些表面化学决定了材料如何与蛋白质相互作用。接下来，pi将通过使用新的温度跳变测量来测量固定蛋白质的折叠率，从而确定这些纳米级特性如何改变蛋白质的稳定性。纳米尺度力测量和亚微米分辨率温度跳跃测量的使用将独特地确定分子尺度界面力场和保护或关闭蛋白质功能的表面化学物质之间的因果关系。该计划将热响应性聚（n-异丙基丙烯酰胺）的先前研究扩展到两性离子涂层，两性离子涂层显示出卓越的抗蛋白质性能和明显的蛋白质/生物相容性，尽管在组成和结构上存在显着差异。分子力测量和转化表面特定温度跳变测量将揭示表面微环境与蛋白质折叠稳定性之间的物理化学耦合。这些研究将弥合纳米级表面化学和固定化蛋白质折叠稳定性之间的差距，并为工程蛋白质保护微环境确定变革性的新设计规则。