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Nanoscale probes for sensing molecular functions in live cells

用于感测活细胞中分子功能的纳米级探针

基本信息

批准号：
10623311
负责人：
Bianxiao Cui
金额：
$ 63.75万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2026-05-31
项目状态：
未结题

项目摘要

Project Summary / Abstract: This MIRA proposal merges two distinct projects supported by R01GM128142, “The role of membrane curvature in surface nanotopography-induced cell functions”, and R01GM125737, “Developing nanoscale electrophysiology sensors for robust intracellular recording”. While the two projects focus on different biological questions, the unifying theme is to develop nanoscale probes to elucidate the cellular machinery in the intricate environment of living cells. In this proposal, we discuss topics along the lines of the parent grants, focusing on the significance of the biological problems, our recent and evolving results, and directions for the future. For the first project, the long-term goal is to understand how membrane curvature regulates biochemical signals that are transmitted through the cell-matrix interface. At the cell-matrix interface, where the cells make physical contact with extracellular matrices, the membrane may be locally deformed by matrix topography or mechanical forces. As it remains a challenge to manipulate nanoscale membrane curvature in live cells, our current understanding of how local membrane curvature affects signal transmission is limited. We propose to use nanotechnology-based precision engineering to control interface membrane curvature in live cells. We seek to understand how cellular processes are affected by membrane curvature and the underlying molecular mechanisms. The knowledge gained will help us understanding how cells interact with extracellular matrix and also help us designing biomaterials for better integration with cells. For the second project, we are developing vertical nanoelectrodes into a robust and easy-to-use electrophysiology tool that can reliably achieve parallel intracellular recording of cardiomyocytes with minimal perturbation. Simultaneous nanoelectrode and patch clamp recordings on same cells confirmed that nanoelectrodes accurately record action potential waveforms for classification and characterization of stem-cell-derived cardiomyocytes. These nanoelectrodes will enable us to understand how in vitro interventions accelerate the maturation of stem-cell-derived cardiomyocyte. Furthermore, nanoelectrodes provide an ideal tool for monitoring the generation and resealing of membrane pores on cardiomyocytes that are prone to membrane rupture due to their large size and strong mechanical contraction. We will use nanoelectrode to investigate how proteins participate in the membrane resealing process. We hope to achieve a broad impact by combining the development of new tools with applications to specific biological systems.

项目摘要/摘要：该 MIRA 提案合并了 R01GM128142 支持的两个不同项目，“膜的作用表面纳米形貌诱导的细胞功能中的曲率”，以及 R01GM125737，“开发纳米级用于强大细胞内记录的电生理学传感器”。虽然这两个项目专注于不同的生物问题的统一主题是开发纳米级探针来阐明复杂的细胞机制活细胞的环境。在本提案中，我们讨论了与家长补助金相关的主题，重点是生物学问题的重要性、我们最近和不断发展的结果以及未来的方向。为了第一个项目，长期目标是了解膜曲率如何调节生化信号通过细胞-基质接口传输。在细胞-基质界面处，细胞在此处进行物理与细胞外基质接触，膜可能会因基质地形或机械力。由于在活细胞中操纵纳米级膜曲率仍然是一个挑战，我们的目前对局部膜曲率如何影响信号传输的理解是有限的。我们建议使用基于纳米技术的精密工程来控制活细胞中的界面膜曲率。我们试图了解细胞过程如何受到膜曲率和潜在分子的影响机制。获得的知识将帮助我们了解细胞如何与细胞外基质相互作用以及还帮助我们设计生物材料以更好地与细胞整合。对于第二个项目，我们正在开发将垂直纳米电极转化为强大且易于使用的电生理学工具，可以可靠地实现并行以最小的扰动对心肌细胞进行细胞内记录。同步纳米电极和贴片对相同细胞的钳记录证实纳米电极准确记录动作电位波形用于干细胞来源的心肌细胞的分类和表征。这些纳米电极将使我们了解体外干预如何加速干细胞来源的心肌细胞的成熟。此外，纳米电极为监测膜的产生和重新密封提供了理想的工具。心肌细胞上的孔洞尺寸较大，机械力强，容易发生膜破裂。收缩。我们将使用纳米电极来研究蛋白质如何参与膜重新密封过程。我们希望通过将新工具的开发与应用程序相结合来实现广泛的影响特定的生物系统。