Tools to Control and Monitor Van der Waals Forces between Nanoparticles: Quantitative Insights on Biological, Environmental, and Fungal Cell Interactions.

随着物质尺寸的减小，物质的行为发生了戏剧性的变化--特别是当尺寸减小到纳米级的时候。这些非常小的物质被称为纳米颗粒，这些纳米颗粒对人类有用。例如，家庭验孕使用纳米颗粒，新冠肺炎疫苗使用纳米颗粒，最先进的电视使用纳米颗粒。纳米颗粒还可用于将材料(例如，药物或遗传物质)输送到细胞。纳米颗粒面临的一个挑战是，它们通常非常不稳定，会聚集在一起，而且这些纳米颗粒团块不具有与单个纳米颗粒相同的性质。因此，这项研究将创造控制纳米颗粒如何聚集在一起的新方法。这项研究是基于之前的工作，表明微小的蛋白质片段可以导致纳米颗粒以可逆的方式组装。因此，可以根据蛋白质的存在来开启和关闭材料的纳米级特性。这项研究将首先研究不同种类的蛋白质，以确定结块和解块是如何发生的。然后，研究人员将研究不同类型的纳米颗粒，以了解可以使用的纳米颗粒类型的范围。活动包括以实验室为基础的研究和计算建模。研究的最后阶段将集中在真菌细胞以及这些纳米颗粒与真菌细胞的相互作用。真菌很重要，因为它们可以致病，可以作为食物食用，也可以用于生物制造。这项研究的结果将是关于如何储存和稳定纳米颗粒的新知识，以及如何利用纳米颗粒控制真菌细胞特性的新知识。当相互排斥的静电和空间作用力被吸引的范德华作用力平衡时，纳米粒子是胶体稳定的。先前的工作表明，二-精氨酸肽可以通过调节这些表面力来诱导可逆的纳米颗粒聚集(从而导致等离子体耦合)。这项研究将对多肽长度、氨基酸序列和纳米颗粒表面如何影响这种可逆聚集产生一致的机制理解。目标1将研究多肽长度和电荷的结构/功能关系：该研究将通过等离子体耦合监测纳米颗粒的聚集和再悬浮，包括在生物和环境介质(如唾液和海水)中。目的2改变纳米颗粒的大小，以确认范德华力的作用，并优化组装/拆卸过程中的颜色变化。目标1和目标2将结合计算建模和实验室分析。目标3将利用这些经验教训来测量聚集的和游离的纳米颗粒作为蛋白酶表达的函数在真菌细胞壁上的相互作用和运输。这项工作将在不同领域创造新的知识：1)等离子体材料如何组装和分解；2)如何在干燥和聚集状态下存储纳米颗粒；3)如何在生物和环境介质中重新分散纳米颗粒；以及4)聚集和游离的纳米颗粒如何与真菌细胞和真菌蛋白酶相互作用。Pi Jokerst和Co-I Miller将通过不同的等离子纳米颗粒制造出“等离子骄傲旗”，并向圣地亚哥的一家拉美裔服务机构以及LGBT+倡导团体传授相关科学知识。通过这些学生小组，PIS活动将有助于留住STEM的LGBT+学生。其他教育目标包括接待来访的暑期学生，他们将与Co-I Pascal.一起学习计算方法。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。

The behavior of matter changes dramatically as the size of the matter decreases—especially when the size decreases to the nanometer regime. These very small pieces of matter are called nanoparticles, and these nanoparticles are useful to people. For example, home pregnancy tests use nanoparticles, Covid-19 vaccines use nanoparticles, and state-of-the-art televisions use nanoparticles. Nanoparticles can also be used to deliver materials (e.g., drugs or genetic material) to cells. One challenge with nanoparticles is that they are often very unstable and clump together, and these clumps of nanoparticles do not have the same properties as individual nanoparticles. Thus, this research will create new ways of controlling how nanoparticles clump together. The research is based on prior work showing that tiny pieces of protein can cause nanoparticles to assemble in a reversible way. Thus, the nano-scale properties of the material can be turned on and off based on the presence of the protein. This research will first study different kinds of protein to determine how the clumping and de-clumping occur. The research will then study different kinds of nanoparticles to understand the range of nanoparticle types that can be used. Activities include both laboratory-based research and computational modeling. A final phase of the research will focus on fungal cells and the interactions of these nanoparticles with fungal cells. Fungi are important because they can cause disease, be consumed as food, or be used for biomanufacturing. The outcome of this research will be new knowledge about how to store and stabilize nanoparticles as well as new knowledge about how to control the properties of fungal cells with nanoparticles. Nanoparticles are colloidally stable when the repulsive electrostatic and steric forces are balanced by the attractive Van der Waals forces. Prior work showed that a di-arginine peptide could induce reversible nanoparticle aggregation (and thus plasmonic coupling) by modulating these surface forces. This research will derive a coherent mechanistic understanding of how the peptide length, amino acid sequence, and nanoparticle surface impact this reversible aggregation. Objective 1 will study the structure/function relationship of peptide length and charge: The research will monitor nanoparticle aggregation and resuspension via plasmonic coupling including in biological and environmental media (e.g., saliva and seawater). Objective 2 will change the nanoparticle size to confirm the role of Van der Waals forces and optimize the color change during assembly/disassembly. Objectives 1 and 2 will combine computational modeling and laboratory assays. Objective 3 will use these lessons learned to measure the interaction and transport of aggregated and free nanoparticles across fungal cell walls as a function of protease expression. This work will create new knowledge in different domains: 1) how plasmonic materials assemble and disassemble; 2) how to store nanoparticles in a dry and aggregated state; 3) how to redisperse nanoparticles in biological and environmental media; and 4) how aggregated and free nanoparticles interact with fungal cells and fungal proteases. PI Jokerst and Co-I Miller will create “plasmonic pride flags” via different plasmonic nanoparticles and teach the underlying science to a Hispanic Serving Institution in SanDiego as well as LGBT+ advocacy groups. Through these student groups, the PIs activities will help retain LGBT+ students in STEM. Additional educational objectives include hosting visiting summer students who will learn computational methods with Co-I Pascal.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.