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。非技术摘要随着农业和制造业在全球范围内的扩张以及全球范围内的健康危机不断出现，生物传感器的发展，允许在各种环境中改进分子检测，对于我们维护人类和生态健康的能力至关重要。纳米颗粒可以重现生物过程以感测分析物，例如局部化学物质或蛋白质，并通过生物分子的合成和分泌进行响应，这将大大提高生物传感应用的功效。为了实现这一目标，NSF的CAREER提案将设计将稳定分子与膜蛋白和蛋白质合成系统结合在一起的颗粒。该项目将绘制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活性。预计拟议的研究将有助于显着改善生物传感平台，可以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检测从脉管系统到地下水的一系列含水环境中的生物分子，从而能够早期检测感染和疾病以及微生物含量。本提案的教育目标将与芝加哥公立学校（CPS）的教师合作制定一项教育计划。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，同时为公立学校小学/中学教师提供重要的教师领导培训和专业网络建设。技术摘要混合膜，由二嵌段共聚物和磷脂组装而成，已成为设计生物传感器，药物输送车辆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性和稳定性得到磷脂与膜蛋白的生物相容性的补充。尽管重要的最近的示范能力的混合膜，将膜蛋白，仍然有一个关键的差距，在知识基础，涉及膜的生物物理特性对膜蛋白和无细胞表达动力学的影响。这些限制在我们的理解的结构-功能关系的合成膜，严重阻碍了效用的合成囊泡作为细胞模拟生物传感器。拟议中的研究预计将有助于膜组成，膜物理性质，和嵌入的膜蛋白和封装的无细胞传感器的活动之间的基本关系。这种贡献是重要的，因为一旦我们建立了这些物质关系，一种新型的膜该奖项反映了NSF的法定使命，并被认为值得通过利用基金会的知识价值和更广泛的评估来支持。影响审查标准。

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.