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.
