Probing and Engineering Cell Membrane with Graphene

随着石墨烯纳米科学的进步，由于其具有诱人的物理、化学和生物学特性，人们对将石墨烯应用于生物和生物医学研究产生了极大的兴趣。研究人员正在努力探索其在药物输送、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，是细胞膜的基本组成部分。然而，由于缺乏探索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有限。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，从而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，从而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，而且还将促进未来跨学科的方法来破译控制细胞膜的分子和细胞机制。此外，这项研究将与一项教育计划相结合，向所有年龄和背景的学生推广科学和工程。私家侦探会和范德比尔特合作吗？美国的科学推广中心（Center for Science Outreach）致力于将研究影响扩大到K-12学生，促进本科生和研究生的跨学科教育和培训，并鼓励女性和在工程和物理领域代表性不足的学生。胆固醇是最重要的脂质分子之一，参与形成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认识还远远不够。最近的研究表明，石墨烯可以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通路和相关的细胞行为。该项目将开发一种基于石墨烯的策略，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学镊子将单个胆固醇分子靠近悬浮的石墨烯晶体管，直接测量它们之间的结合力。基于胆固醇与石墨烯分子界面的基本知识，超快石墨烯场效应晶体管将被用于控制细胞膜内局部胆固醇浓度。同时，细胞结构将通过荧光显微镜监测。这些基础研究不仅将深入了解石墨烯与胆固醇之间的键合机制，而且还将揭示胆固醇在细胞膜中的动力学和分布，为未来的细胞工程开辟全新的途径。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。

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.