Understanding the interaction of 2D particles with phospholipid membranes

了解二维粒子与磷脂膜的相互作用

• 批准号: 2114568
• 负责人: Joseph Samaniuk
• 金额: $ 32.4万
• 依托单位: Colorado School of Mines
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2114568&HistoricalAwards=false
• 关键词: Understanding; interaction; 2D; particles; phospholipid

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.

在这个项目中进行的研究将使人们更好地理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，而膜将由肺部天然存在的脂质分子组成。石墨烯是一种被称为二维粒子的更广泛的粒子类别的代表，它越来越多地应用于电池、混凝土、各种涂料甚至安全口罩等消费品中。随着二维粒子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，二维粒子可以被整合到产品中，在这些产品中，与肺中发现的脂肪性质相似的脂质被用来制造乳剂，如油漆和化妆品。尽管许多二维粒子（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尚不清楚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粒子存在时脂质膜结构的变化。这些结果可以让我们更好地理解二维粒子影响生物膜的方式，尤其是那些在肺部发现的，但它们也可以让我们更好地理解二维粒子在含脂消费品中的使用方式。该项目还包括与当地一所小学的外展部分，在那里，首席研究员将与有特殊学习障碍的学生一起使用动手演示，说明与工作相关的重要物理概念，包括表面张力。其目标是增加那些由于特殊学习障碍而可能回避技术领域的学生对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理解二维粒子与磷脂单层的相互作用。二维粒子是一类在可用化学物质方面迅速膨胀的纳米粒子。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，包括单层和双层膜，在生物学中无处不在，并受到纳米粒子存在的影响，尽管这些膜与二维粒子之间相互作用的性质尚不清楚。核心假设是，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，堆积的颗粒层数和膜面积密度，这与颗粒在膜中的物理位置（例如在脂质尾部上冲浪或嵌入）以及颗粒对周围磷脂结构的影响有关。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。所使用的材料将是石墨烯和磷脂双棕榈酰磷脂酰胆碱。这项工作的一个重要贡献是在模型系统上生成大量的实验数据，用于比较计算结果，这是迄今为止理解二维粒子与生物膜相互作用的一个限制因素。这项工作的另一个成果将是提高对二维粒子如何影响磷脂结构的理解，它们与横向相互作用，这种行为可以改变膜的界面流变性能。这项工作的第三个贡献将是了解多层，堆叠的二维粒子层与膜的相互作用与单层的不同。虽然二维粒子通常被认为是单层的，但热力学驱动单层堆叠。因此，了解多层膜与生物膜的相互作用是相关的，因为无论这种相互作用是来自无意暴露于二维粒子，还是来自未来生物治疗应用中有意使用这些粒子，这都可能是生理学上相关的。预计在利用石墨烯作为二维粒子模型的这项工作中所学到的知识可能会推广到不同化学性质的二维粒子，因为涉及界面上球形粒子的研究表明，粒子形状是预测流体-流体界面上粒子动力学的一个主要因素。该项目包括一个外联部分，研究者将访问当地一所小学，为有特殊学习障碍的学生群体演示界面现象的基本概念，如表面张力。这些学生倾向于避免STEM领域，因为他们被贴上了学习障碍的标签。目标是通过向他们展示他们完全有能力理解物理中的复杂概念来提高他们对STEM职业的长期兴趣。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。