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

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。随着农业和制造业在全球范围内的扩张以及世界范围内的健康危机继续出现，开发能够在各种环境中改进分子检测的生物传感器对于我们维持人类和生态健康的能力至关重要。纳米粒子可以概括生物过程来感知分析物，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 CAREER计划将设计包含稳定分子、膜蛋白和蛋白质合成系统的颗粒。该项目将绘制出所设计颗粒的独特机械和物理特性如何影响所设计颗粒的传感能力和生物反应性。预计该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，克服先前将其部署为自主系统的障碍。这一进展将使研究人员和临床医生能够在一系列含水环境中检测生物分子，从脉管系统到地下水，从而允许早期检测感染和疾病以及微生物含量。该提案的教育目标是与芝加哥公立学校（CPS）的教师合作开发一个教育项目。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，同时为公立学校小学/中学教师提供重要的教师领导培训和专业网络建设。由二嵌段共聚物和磷脂组装而成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柔韧性和稳定性被磷脂与膜蛋白的生物相容性所补充。尽管最近在杂交膜整合膜蛋白的能力方面有了重要的证明，但关于膜生物物理特性对膜蛋白和无细胞表达动力学的影响的知识库仍然存在一个关键的空白。在我们对合成膜的结构-功能关系的理解上的这些限制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、嵌入膜蛋白和被封装的无细胞传感器的活性之间的基本关系做出贡献。这一贡献是重要的，因为一旦我们建立了这些材料关系，就可以设计出一类新的基于膜的设备，这将提供一种方法来动态绘制血管和水生环境中的化学和环境变化，否则很难进入。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.