Nanomechanical studies of cells and biomolecules

细胞和生物分子的纳米力学研究

• 批准号: 10406574
• 负责人: Ozgur Sahin
• 金额: $ 40.56万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406574
• 关键词: Address; Atomic Force Microscopy; Biologic Characteristic; Biological Process; Biology; Cell membrane; Cell model; Cells; Chemicals; Coupling; Crystallization; Data; Development; Disease; Freezing; Goals; Image; Ion Channel Gating; Laboratories; Mathematics; Measures; Mechanics; Membrane Proteins; Methods; Modeling; Molecular; Morphology; Organelles; Pattern; Physiological; RNA; Research; Research Personnel; Resolution; Role; Sampling; Shapes; Techniques; Technology; Theoretical model; Vision; Work; base; biological systems; biophysical model; cellular imaging; imaging modality; interest; mechanical behavior; mechanical properties; nanomechanics; nanoscale; prevent; programs; protein complex; structural biology

Abstract The research in our laboratory is centered on the development of force-based mechanical approaches to biomolecular and cellular imaging, and leveraging these capabilities to study a number of questions in biomolecular dynamics and cells mechanics. Our approach to imaging offers new capabilities in probing chemical, mechanical and electrical characteristics of biological systems from molecules to cells. In biomolecular imaging, we focus on problems in structural biology that can benefit from direct imaging in physiologically relevant conditions where mechanical approaches like atomic force microscopy (AFM) have advantages. We currently develop an AFM-based method to image dynamics of RNA/protein complexes and membrane proteins with Angstrom scale resolution. In cell mechanical studies, we recently developed a cell stiffness imaging method that provided unprecedented spatial resolution, which helped reveal nanoscale patterns in cell stiffness that are described by precise mathematical relationships. Existence of these patterns are not predicted by the current quantitative models of cell mechanics. We developed a new model that not only explained our findings, but also made new testable predictions that we subsequently confirmed. These molecular and cellular studies shape the current research goals in our laboratory. On the biomolecular imaging front, our goal for the next five years is to develop our technology to achieve imaging of biomolecular dynamics in physiologically relevant conditions with Angstrom- scale resolution. Currently, such high-resolution data is mainly coming from methods that work with frozen or crystallized samples, which prevent observations of biomolecular dynamics. On the cell mechanics front, our goals for the next five years include further developing our cell mechanical model to address a large discrepancy between results measured by different methods used by researchers. We believe the discrepancy is not due to technical problems of various methods, but rater due to underlying assumptions about contact mechanics of cells, that is, a conceptual issue. Addressing this discrepancy can help better predict cell mechanical behavior in physiological contexts. We are also interested in investigating electromechanical coupling in cell membranes and have already built a uniquely suited experimental setup to probe electromechanical coupling in cell membranes. We are motivated by our recent observations of strong coupling effects and potential effects of coupling on gating of ion channels and the morphology of membranous organelles. Overall, the vision of our research program is set by the important roles of nanoscale mechanical interactions in biology, and we develop biophysical models and experimental capabilities to realize our vision.

抽象的 我们实验室的研究重点是基于力的机械的开发 生物分子和细胞成像方法，并利用这些能力来研究 生物分子动力学和细胞力学方面的问题数量。我们的成像方法 提供了探测化学、机械和电气特性的新功能 从分子到细胞的生物系统。在生物分子成像中，我们重点关注以下问题： 可以从生理相关条件下的直接成像中受益的结构生物学 其中原子力显微镜 (AFM) 等机械方法具有优势。我们 目前正在开发一种基于 AFM 的方法来对 RNA/蛋白质复合物的动态进行成像 具有埃级分辨率的膜蛋白。在细胞力学研究中，我们最近 开发了一种细胞硬度成像方法，提供了前所未有的空间分辨率， 这有助于揭示细胞硬度的纳米级模式，这些模式可以通过精确描述 数学关系。当前的情况无法预测这些模式的存在 细胞力学的定量模型。我们开发了一个新模型，它不仅解释了我们的 发现，但也做出了我们随后证实的新的可检验的预测。这些 分子和细胞研究塑造了我们实验室当前的研究目标。上 在生物分子成像前沿，我们未来五年的目标是开发我们的技术 使用 Angstrom- 在生理相关条件下实现生物分子动力学成像 尺度分辨率。目前，这种高分辨率的数据主要来自于有效的方法 使用冷冻或结晶的样品，这会妨碍生物分子动力学的观察。在 在细胞力学方面，我们未来五年的目标包括进一步开发我们的细胞 力学模型来解决不同测量结果之间的巨大差异 研究人员使用的方法。我们认为这种差异不是由于技术问题造成的 各种方法，但由于有关细胞接触力学的基本假设而进行评估， 也就是说，一个概念问题。解决这种差异可以帮助更好地预测细胞机械性能 生理背景下的行为。我们也有兴趣研究机电 耦合在细胞膜中，并已经建立了一个独特的适合的实验装置 探测细胞膜中的机电耦合。我们受到最近的激励 强耦合效应和耦合对离子门控的潜在影响的观察 通道和膜细胞器的形态。总体而言，我们的研究愿景 该计划是根据纳米级机械相互作用在生物学中的重要作用而设定的，我们 开发生物物理模型和实验能力来实现我们的愿景。