Nanomechanical studies of cells and biomolecules

细胞和生物分子的纳米力学研究

基本信息

批准号：
10668957
负责人：
Ozgur Sahin
金额：
$ 40.62万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
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

项目摘要

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集中于基于力的机械的发展生物分子和细胞成像的方法，并利用这些能力研究生物分子动力学和细胞力学中的问题数量。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，我们专注于结构生物学，可以从生理相关条件下直接成像中受益原子力显微镜（AFM）等机械方法具有优势。我们目前开发了一种基于AFM的方法来图像RNA/蛋白质复合物的动力学和膜蛋白具有分辨率。在细胞机械研究中，我们最近开发了一种细胞刚度成像方法，该方法提供了前所未有的空间分辨率，这有助于揭示细胞刚度中的纳米级模式数学关系。这些模式的存在并不能由当前预测细胞力学的定量模型。我们开发了一种新模型，不仅解释了我们的调查结果，但也做出了我们随后确认的新的可测试预测。这些分子和细胞研究塑造了我们实验室中当前的研究目标。在生物分子成像方面，我们未来五年的目标是开发我们的技术在生理相关的条件下实现生物分子动力学成像，比例分辨率。目前，这样的高分辨率数据主要来自起作用的方法用冷冻或结晶的样品，可防止观察到生物分子动力学。在细胞力学方面，我们接下来五年的目标包括进一步开发我们的细胞机械模型解决了通过不同的结果之间的巨大差异研究人员使用的方法。我们认为差异不是由于各种方法，但由于对细胞接触力学的基本假设而引起的评估者，也就是说，这是一个概念上的问题。解决此差异可以帮助更好地预测细胞机械生理环境中的行为。我们也有兴趣研究机电在细胞膜中耦合，并且已经为细胞膜中的探针机电耦合。我们最近的动机观察强耦合效应和耦合对离子门控的潜在影响通道和膜细胞器的形态。总体而言，我们的研究愿景程序是由纳米级机械相互作用在生物学中的重要作用所设定的，我们开发生物物理模型和实验能力以实现我们的愿景。