Understanding the interaction of 2D particles with phospholipid membranes

该项目正在进行的研究将导致更好地了解小颗粒与由脂质分子组成的生物和非生物膜相互作用的方式。将被研究的特定颗粒是石墨烯，膜将由肺中天然存在的脂质分子组成。石墨烯代表了一种更广泛的称为二维颗粒的颗粒，这种颗粒越来越多地用于消费品，如电池，混凝土，各种涂料，甚至安全口罩。随着二维颗粒的使用和可用性的增加，它们与各种能力的生物膜（包括肺内的生物膜）的相互作用可能会增加。此外，二维颗粒可以被掺入到产品中，其中与肺中发现的脂质性质相似的脂质用于产生乳液，如油漆和化妆品。虽然许多二维颗粒（如石墨烯）不会与脂质发生化学反应，但有证据表明它们与脂质膜的相互作用可以在微观水平上以不了解的方式改变膜的结构。本研究旨在通过实验和计算机模拟来表征二维颗粒存在下脂质膜结构的变化。这些结果可以更好地理解二维颗粒影响生物膜的方式，特别是在肺部发现的生物膜，但它们也可以更好地理解二维颗粒可用于含脂质消费品的方式。该项目还包括一个与当地一所小学的外联部分，在那里，主要研究员将与有特殊学习障碍的学生一起工作，使用动手示范，说明与工作有关的重要物理概念，包括表面张力。目标是提高那些可能因为特定学习障碍而避免技术领域的学生对STEM职业的长期兴趣。这项工作旨在通过实验和分子动力学模拟来了解二维颗粒与磷脂单层的相互作用。二维颗粒是一类在可用化学物质方面迅速膨胀的纳米颗粒。随着二维材料数量的增加和应用的扩展，这些材料与生物学的交叉，无论是有意还是无意，将变得更加普遍。磷脂膜，包括单层和双层，在生物学中是普遍存在的，并且受到纳米颗粒的存在的影响，尽管这些膜和二维颗粒之间的相互作用的性质尚不清楚。中心假设是，与磷脂单层接触的二维颗粒的横向扩散取决于许多变量，包括颗粒化学、堆叠颗粒层的数量和膜面积密度，并且这与颗粒在膜中的物理位置（例如，在脂质尾上冲浪与嵌入），以及颗粒对周围磷脂结构的影响。该方法将是实验和计算，利用粒子合成技术，各种形式的显微镜，和分子动力学模拟。使用的材料将是石墨烯和磷脂二棕榈酰磷脂酰胆碱。 这项工作将作出的一个重大贡献是产生大量的实验数据的模型系统与计算结果进行比较，一个限制因素，迄今在了解二维粒子与生物膜的相互作用。这项工作的另一个产品将是一个更好的理解如何二维颗粒影响磷脂的结构，他们横向相互作用，一种行为，可以改变膜的界面流变特性。这项工作的第三个贡献将是了解二维颗粒的多个堆叠层与膜的相互作用与单层不同。虽然二维粒子通常被认为是单分子层，但热力学驱动单分子层堆叠。因此，理解多层膜与生物膜的相互作用是相关的，因为这可能是生理相关的，无论相互作用是来自于无意中暴露于二维颗粒，还是来自于在未来生物膜应用中有意使用颗粒。预计在利用石墨烯作为模型二维颗粒的这项工作中所学到的东西将可能推广到不同化学物质的二维颗粒，因为涉及界面处的球形颗粒的研究表明，颗粒形状是预测流体-流体界面处颗粒动力学的主要因素。该项目包括一个外联部分，调查员将访问当地一所小学，进行实际演示，说明界面现象的基本概念，如有特殊学习障碍的学生群体的表面张力。这些学生往往会因为标记的学习障碍而避开STEM领域。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The research being performed in this project will lead to a better understanding of the way small particles interact with membranes, both biological and non-biological, composed of lipid molecules. The specific particles that will be studied are graphene, and the membranes will be comprised of a lipid molecule naturally found in the lungs. The graphene is representative of a broader class of particles called two-dimensional particles, which are increasingly being utilized in consumer products such as batteries, concrete, various coatings, and even safety masks. As the uses and availability of two-dimensional particles increases, their interaction with biological membranes in various capacities, including those within the lungs, will likely increase. In addition, two-dimensional particles can be incorporated into products where lipids similar in nature to those found in lungs are used to create emulsions such as paints, and cosmetics. Although many two-dimensional particles such as graphene will not undergo chemical reactions with lipids, there is evidence that their interaction with lipid films can alter the structure of the film at a microscopic level in ways that are not understood. This research seeks to characterize those alterations in lipid film structure in the presence of two-dimensional particles with both experiments and computer simulations. The results can lead to a better understanding of the way two-dimensional particles influence biological membranes, especially those found in the lungs, but they can also lead to a better understanding of the ways two-dimensional particles can be used in lipid-containing consumer products. The project also includes an outreach component with a local primary school where the principal investigator will work with students with specific learning disabilities using hands-on demonstrations that illustrate important physics concepts relevant to the work, including surface tension. The goal is to increase the long-term interest in STEM careers of those students who may avoid technical fields because of a specific learning disability.This work seeks to understand the interaction of two-dimensional particles with phospholipid monolayers using experiments and molecular dynamics simulations. Two-dimensional particles are a class of nanoparticle that is rapidly expanding in terms of the available chemistries. As the number of two-dimensional materials increases, and the applications expand, the intersection of these materials with biology, either intentionally or unintentionally, will become more prevalent. Phospholipid membranes, including monolayers and bilayers, are ubiquitous in biology, and are influenced by the presence of nanoparticles, although the nature of the interaction between these membranes and two-dimensional particles is not understood. The central hypothesis is that lateral diffusion of two-dimensional particles in contact with phospholipid monolayers is dependent on a number of variables, including particle chemistry, the number of stacked particle layers, and the membrane area density, and that this is related to both the physical position of the particle in the membrane (e.g. surfing on lipid tails vs embedded), and the influence the particle has on the surrounding phospholipid structure. The approach will be both experimental and computational, making use of particle synthesis techniques, various forms of microscopy, and molecular dynamics simulations. The materials utilized will be graphene, and the phospholipid dipalmitoylphosphatidylcholine. One significant contribution that this work will make is the generation of a large amount of experimental data on a model system with which to compare computational results, a limiting factor thus far in understanding the interaction of two-dimensional particles with biological membranes. Another product of this work will be an improved understanding of how two-dimensional particles influence the structure of phospholipids that they interact with laterally, a behavior that can change the interfacial rheological properties of the membrane. A third contribution of this work will be to understand how multiple, stacked layers of two-dimensional particles interacts differently with membranes than single layers. Although two-dimensional particles are often thought of as single monolayers, thermodynamics drive monolayers to stack. As a consequence, it is relevant to understand the interaction of multilayers with biological membranes, since this is likely to be physiologically relevant whether the interaction derives from an unintended exposure to two-dimensional particles, or from an intentional use of the particles in a future biotherapeutic application. It is expected that what is learned in this work utilizing graphene as a model two-dimensional particle will likely be generalizable to two-dimensional particles of different chemistries since research involving spheroidal particles at interfaces indicates that particle shape is a major factor in predicting the dynamics of the particles at fluid-fluid interfaces. The project includes an outreach component where the investigator will visit a local primary school to perform hands-on demonstrations that illustrate basic concepts in interfacial phenomena such as surface tension for groups of students with specific learning disabilities. Such students tend to avoid STEM fields because of a labeled learning disability. The goal is to increase their long-term interest in STEM careers by showing them that they are fully capable of understanding complex concepts in physics.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.