CAREER: Hybrid membranes as platforms for biomolecule detection, synthesis, and transport

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。非技术总结随着农业和制造业在全球范围内的扩张和全球范围内健康危机的持续出现，生物传感器的发展对于我们维持人类和生态健康的能力至关重要。纳米颗粒可以概括生物过程，感知分析物，如局部化学物质或蛋白质，并通过生物分子的合成和分泌做出反应，将极大地提高生物传感应用的效率。为了实现这一目标，NSF的这份职业提案将设计将稳定分子与膜蛋白质和蛋白质合成系统结合在一起的颗粒。该项目将绘制设计颗粒的独特机械和物理属性如何影响设计颗粒的传感能力和生物反应性。预计拟议的研究将有助于显著改进生物传感平台，从而提高生物检测的灵敏度和增强无细胞系统的稳定性，克服以前作为自主系统部署的障碍。这一进展将使研究人员和临床医生能够检测从血管到地下水的一系列含水环境中的生物分子，从而能够及早检测到感染和疾病以及微生物含量。该提案的教育目标将与芝加哥公立学校(CPS)的教师合作开发一项教育计划。该项目将为STEM研究生提供急需的社区参与培训和教学技能，同时为公立学校中小学教师提供重要的教师-领导者培训和专业网络建设。技术摘要由两嵌段共聚物和磷脂组装的杂化膜已成为设计生物传感器、药物输送载体和生物反应器的潜在强大材料界面。聚合物赋予磷脂膜的化学灵活性和稳定性被磷脂与膜蛋白的生物相容性所赞誉。尽管最近关于杂化膜结合膜蛋白的能力有了重要的证明，但关于膜的生物物理性质对膜蛋白和无细胞表达动力学的影响的知识基础仍然存在一个关键的缺口。这些限制了我们对合成膜结构-功能关系的理解，严重阻碍了合成囊泡作为细胞模拟生物传感器的应用。这项拟议的研究有望为膜组成、膜物理性质和包埋膜蛋白和微囊化无细胞传感器的活性之间的基本关系做出贡献。这一贡献意义重大，因为一旦我们建立了这些材料关系，就可以设计一种新的基于膜的设备，提供一种动态绘制血管和水环境中化学和环境变化的方法，而这些变化是以其他方式难以获得的。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).Non-Technical SummaryAs agriculture and manufacturing expand globally and world-wide health crises continue to arise, the development of biosensors that allow improved molecular detection in a variety of settings are critical for our ability to maintain human and ecological health. Nanoparticles that can recapitulate biological processes to sense analytes, such as a local chemical or protein, and respond via the synthesis and secretion of biomolecules, would dramatically improve the efficacy of biosensing applications. Towards this goal, this NSF CAREER proposal, will design particles that incorporate stabilizing molecules alongside membrane proteins and protein synthesis systems. The project will map how the unique mechanical and physical properties of the particles designed impact the sensing capabilities and bioreactivity of the designed particles. The proposed research is expected to contribute a markedly improved biosensing platform that could generate improved sensitivity of biological detection and enhanced stability of cell-free systems, overcoming previous obstacles to their deployment as autonomous systems. This advance will enable researchers and clinicians to detect biological molecules in an array of water-containing environments, from vasculature to ground water, allowing for the early detection of infection and disease to microbial content. The educational objective of this proposal will develop an educational program partnering with teachers from Chicago Public Schools (CPS). This program will provide much-needed community engagement training and pedagogical skills for STEM graduate students, while providing important teacher-leader training and professional network building for public school elementary/middle grade teachers.Technical SummaryHybrid membranes, assembled from diblock copolymers and phospholipids, have emerged as a potentially powerful material interface to design biosensors, drug delivery vehicles, and bioreactors. The chemical flexibility and stability that polymers impart to phospholipid membranes is complimented by the biological compatibility of phospholipids with membrane proteins. In spite of important recent demonstrations on the capacity of hybrid membranes to incorporate membrane proteins, there is still a critical gap in the knowledge base that pertains to the effect of membrane biophysical properties on membrane protein and cell-free expression dynamics. These limitations in our understanding of the structure-function relationship of synthetic membranes have seriously hampered the utility of synthetic vesicles as cellular mimetic biosensors. The proposed research is expected to contribute fundamental relationships between membrane composition, membrane physical properties, and the activity of embedded membrane proteins and encapsulated cell-free sensors. This contribution is significant because once we have established these material relationships, a new class of membrane-based devices can be designed that will provide a way to dynamically map chemical and environmental changes in vascular and aquatic environments that have been difficult to otherwise access.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.