Probing and Engineering Cell Membrane with Graphene

用石墨烯探测和改造细胞膜

• 批准号: 1810088
• 负责人: Sharon Weiss
• 金额: $ 35.32万
• 依托单位: Vanderbilt University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1810088&HistoricalAwards=false
• 关键词: Probing; Engineering; Cell; Membrane; Graphene

With the advances in graphene nanoscience there has been tremendous interest in applying graphene for biological and biomedical studies, due to its attractive physical, chemical and biological properties. Significant research endeavors are ongoing to explore its potential applications for drug delivery, tissue engineering, biosensing, diagnostic imaging. Cholesterol is an organic molecule, an essential building block for cell membranes. However, the knowledge on the cell membrane and its cholesterol contents is limited due to the lack of methods to explore membrane cholesterol dynamics and its relationship with other biomolecules. Recent studies have shown that graphene can directly and selectively interact with cholesterol in cell membranes and subsequently modulate the cellular structure and function. In this project, the intermolecular interactions between cholesterol and graphene will be directly measured via dual-trap optical tweezers at the single-molecule level. Moreover, ultrafast graphene field effect transistors will be utilized to explore the dynamics and distribution of cholesterol in cell membranes and then engineer cellular structure and function. These fundamental studies will not only provide new insights into mechanical coupling between biomolecules and nanomaterials, but also promote future interdisciplinary approaches for deciphering molecular and cellular mechanisms governing cell membranes. . In addition, this research will be integrated with an educational plan to promote science and engineering to students of all ages and backgrounds. The PI will coordinate with Vanderbilt?s Center for Science Outreach to extend research impact to K-12 students, foster interdisciplinary education and training to undergraduate and graduate students, and encourage women and underrepresented students in engineering and physics. Cholesterol is one of the most important lipid molecules involved in various interactions that shape the architecture and functionality of the cell membrane. However, the understanding of the cell membrane and its cholesterol contents is far from complete. Recent studies have suggested that graphene can be utilized to directly and precisely manipulate the local cholesterol concentration in cell membranes and thus control specific transmembrane signaling pathways and associated cell behavior. This project will develop a graphene-based strategy to manipulate cellular structure and function with high spatiotemporal resolution. The approach is to use dual-trap optical tweezers to bring a single cholesterol molecule close to a suspended graphene transistor to directly measure the binding force between them. Based on the fundamental knowledge of molecular interface between cholesterol and graphene, ultrafast graphene field effect transistors will be used to manipulate local cholesterol concentration in the cell membrane in a controlled way. Simultaneously, the cellular structure will be monitored via fluorescence microscopy. These fundamental studies will not only provide an in-depth understanding of the bonding mechanisms between graphene and cholesterol, but also shed light on the knowledge of cholesterol dynamics and distribution in cell membranes, opening up entirely new avenues for future cellular engineering.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.

随着石墨烯纳米科学的发展，由于石墨烯具有诱人的物理、化学和生物学特性，人们对石墨烯在生物和生物医学研究中的应用产生了极大的兴趣。大量的研究工作正在进行中，以探索其在药物输送、组织工程、生物传感、诊断成像等方面的潜在应用。 胆固醇是一种有机分子，是细胞膜的重要组成部分。然而，由于缺乏研究细胞膜胆固醇动力学及其与其他生物分子关系的方法，对细胞膜及其胆固醇含量的认识是有限的。最近的研究表明，石墨烯可以直接和选择性地与细胞膜中的胆固醇相互作用，并随后调节细胞的结构和功能。在这个项目中，胆固醇和石墨烯之间的分子间相互作用将通过双阱光镊在单分子水平上直接测量。此外，超快石墨烯场效应晶体管将用于探索胆固醇在细胞膜中的动力学和分布，然后设计细胞结构和功能。这些基础研究不仅将为生物分子和纳米材料之间的机械耦合提供新的见解，而且还将促进未来的跨学科方法，用于破译控制细胞膜的分子和细胞机制。.此外，这项研究将与教育计划相结合，以促进科学和工程的所有年龄和背景的学生。私家侦探会和范德比尔特合作？该中心的科学推广，以扩大研究的影响，以K-12学生，促进跨学科的教育和培训，本科生和研究生，并鼓励妇女和代表性不足的学生在工程和物理。胆固醇是最重要的脂质分子之一，参与塑造细胞膜结构和功能的各种相互作用。 然而，对细胞膜及其胆固醇含量的了解还远未完成。最近的研究表明，石墨烯可用于直接和精确地操纵细胞膜中的局部胆固醇浓度，从而控制特定的跨膜信号传导途径和相关的细胞行为。该项目将开发基于石墨烯的策略，以高时空分辨率操纵细胞结构和功能。该方法是使用双阱光镊将单个胆固醇分子靠近悬浮的石墨烯晶体管，以直接测量它们之间的结合力。基于胆固醇和石墨烯之间的分子界面的基本知识，超快石墨烯场效应晶体管将用于以受控的方式操纵细胞膜中的局部胆固醇浓度。同时，将通过荧光显微镜监测细胞结构。这些基础研究不仅将深入了解石墨烯和胆固醇之间的结合机制，还将揭示胆固醇在细胞膜中的动力学和分布，该奖项反映了NSF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进行评估，被认为值得支持的搜索.