Giant Polymer Brushes: How Fluid-Like Hyaluronan Brushes Minimize Biofilm Adhesion

通过改变表面的性质所能达到的效果令人惊讶。当制成疏水性材料时，表面可以排斥水，例如，可以保护纸张或木材免受水分侵入和损坏。当与特定气体或生物分子发生反应时，它可以成为超灵敏的探测器，例如冠状病毒颗粒的生物传感器。控制表面特性的一种非常成功的方法是，将聚合物以如此高的密度固定在表面，这样它们就会因相邻聚合物的拥挤而排列并伸展出表面。这种结构被称为聚合物刷。聚合物刷在各种各样的实际应用中得到了广泛的应用。这项拨款有双重科学目的。第一个目的是利用自然界的分子机器，通过直接从表面生长分子来生产聚合物刷子。令人惊讶的是，这项新技术可以生产出比传统技术厚近100倍的聚合物刷层。这为材料的战略设计提供了令人兴奋的新特性。第二个目的是解决一个困扰人类的重要问题：生物膜的形成，即顽固的细菌群落，它们被自己制造的类似粘液的粘稠物所保护。聚合物刷是一种流行的延缓生物膜附着的策略，但最终，它们仍然失败。受到有希望的初步结果的激励，该项目在这项资助中探索了巨型分子机器产生的刷子及其相应的流体状界面是否可以导致细菌无法附着的表面-这是一种最近才在其他情况下引入的新策略。为了确保任何仍能附着的细菌被迅速清除，研究人员将在大体积的牙刷中嵌入抗菌剂。总之，这些措施将导致一种令人兴奋的新型聚合物刷技术的成熟，解决细菌感染和人造材料污染的古老问题。在推广和教育方面，柯蒂斯实验室将发布一系列关于科学、生物材料和这个跨学科项目应用的有趣的卡通短片。这些视频将在youtube频道上分享并广泛传播。主题将包括抗菌材料、生物膜、聚合物刷和制造聚合物的分子机器。摘要聚合物刷是一种重要的工程界面工具，在药物输送、植入物、催化和抗微生物材料等各种应用中都有应用。这笔资金将集中在确定柯蒂斯实验室最近建立的一种非传统的超厚聚合物刷的防污性能的来源和范围。这种由透明质酸合成酶制成的刷子是迄今为止最厚的刷子，厚度几乎增加了两个数量级。初步结果表明，这些透明质酸刷可以驱除细菌，防止生物膜粘附长达一周，比透明质酸膜要好一个数量级，后者被认为具有优越的防污性能。柯蒂斯实验室将测试一个假设，即这些刷子的优越性能源于它们的流体状界面，类似于最近引入的其他非常成功的抗生物膜应用材料。此外，他们将通过系统研究其对刷枝接枝密度和分子量的依赖来优化刷的防污性能。最后，为了最大限度地提高刷的抗生物膜性能，他们将在整个材料中固定杀菌剂，以创建具有最佳抗微生物性能的多功能生物界面。更广泛地说，这项研究将有助于新型聚合物刷的持续发展，有望在材料科学中找到更广泛的应用。在推广和教育方面，柯蒂斯实验室将发布一系列关于该项目的科学、生物材料和应用的有趣的卡通短片。这些视频将在youtube频道上分享并广泛传播。主题将包括防污材料、生物膜、聚合物刷等。此外，柯蒂斯博士将继续努力增加STEM的多样性，利用这一资助期间与历史上的黑人学院和大学的教师、顾问和学生建立联系并建立持久的关系。这些活动的主要目标是：(1)建立有效的关系，以帮助改善少数民族学生的招募和保留；(2)通过对话学习如何改善乔治亚理工学院的氛围，使其对有色人种学生更加欢迎和支持。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。

Non-Technical AbstractIt is surprising how much can be accomplished by changing the properties of a surface. When made hydrophobic, a surface repels water and can, for example, protect paper or wood from moisture intrusion and damage. When made reactive to a specific gas or biomolecule, it can become an ultra-sensitive detector, for example a biosensor for coronavirus particles. One very successful way to control surface properties, so as to create designer materials like those described above, is to anchor polymers to the surface at such a high density that they align and stretch away from the surface because of crowding by their neighbors. This configuration is known as a polymer brush. Polymer brushes have been used in a stunning variety of practical applications. This grant has a twofold scientific purpose. The first purpose is to leverage nature’s molecular machines to produce polymer brushes by growing molecules directly from the surface. Amazingly, this new technology enables the production of polymer brush layers nearly one hundred times thicker than the those achievable with conventional techniques. This presents exciting new properties for the strategic design of materials. The second purpose is to address an important problem that plagues mankind: the formation of biofilms – that is communities of recalcitrant bacteria entrenched and protected in a mucous-like goo of their own making. Polymer brushes are a popular strategy to delay biofilm attachment but ultimately, they still fail. Motivated by promising preliminary results, the project explores in this grant whether the giant molecular-machine generated brush and its corresponding fluid-like interface can lead to a surface that the bacteria are unable to tether to – a new strategy only recently introduced in other contexts. To ensure that any bacteria which still manage to adhere are quickly eliminated, the researchers will embed antimicrobials within the large volume of the brush. Together, these measures will result in the maturation of an exciting new polymer brush technology addressing the age-old problem of bacterial infection and contamination of man-made materials. In outreach and education, the Curtis lab will publish a series of short playful cartoon videos about the science, biomaterials, and applications of this interdisciplinary project. The videos will be shared on a You Tube channel and disseminated widely. Topics will include anti-microbial materials, biofilms, polymer brushes, and molecular machines for making polymers. Technical AbstractPolymer brushes are an important tool for engineering interfaces in a variety of applications such as drug delivery, implants, catalysis, and anti-microbial materials. This grant will focus on pinpointing the origin and extent of the anti-fouling properties of a non-traditional, ultra-thick polymer brush recently established in the Curtis lab. Fabricated by surfaces coated with hyaluronan synthase, the enzyme-derived brushes are the thickest ever created by almost two orders of magnitude. Preliminary results demonstrate that these hyaluronan brushes repel bacteria and prevent biofilm adhesion for up to a week, performing an order of magnitude better than hyaluronan films, which are recognized as having superior anti-fouling properties. The Curtis lab will test the hypothesis that the superior performance of theses brushes arises from their fluid-like interface, similar to other recent very successful materials introduced for anti-biofilm applications. In addition, they will optimize the anti-fouling performance of the brushes with systematic studies of its dependence on brush grafting density and molecular weight. Lastly, to maximize the anti-biofilm properties of the brush, they will immobilize biocides throughout the material to create a multi-functional biointerface with optimal anti-microbial performance. More broadly, this research will contribute to the continued development of a new class of polymer brush, which is expected to find broader applications in materials science. In outreach and education, the Curtis lab will publish a series of short playful cartoon videos about the science, biomaterials, and applications of this project. The videos will be shared on a You Tube channel and disseminated widely. Topics will include anti-fouling materials, biofilms, polymer brushes, etc. Additionally, Dr. Curtis will continue her efforts to increase diversity in STEM by using the period of this grant to establish contacts and build lasting relationships with faculty, advisors, and students at historically Black colleges and universities. These activities have the primary goals of (1) building effective relationships to help improve recruitment and retention of minority students and (2) learning through conversations how to enhance the climate at Georgia Tech to make it more welcoming and supportive for students of color.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.