Imaging and Controlling Molecular Forces in Live Cell

我的研究项目旨在了解物理力量如何调节细胞行为。机械力最近被发现在生物系统的发育和功能中起着至关重要的作用。因此，理解和控制细胞微环境中的机械力为发现和生物技术发展提供了重要的机会。细胞与环境的相互作用主要是通过粘附作用，细胞表面的粘附蛋白与环境中其他细胞或物质上的受体结合。细胞粘附研究的一个特别重要的领域是白细胞和循环肿瘤细胞的滚动粘附级联，这是炎症反应和癌症转移的关键过程。虽然现在可以很容易地在整个细胞尺度上测量附着力，但在分子水平上对附着力的动力学知之甚少。理解和测量分子力是机械生物学面临的主要挑战之一。特别是，在分子水平上，对滚动粘附力的大小、分布、化学计量、激活状态、信号传导和协同效应的定量认识很少。缺乏分子水平上的机制细节阻碍了对细胞行为的进一步理解和控制。我的研究项目旨在开发新技术，以可视化和控制在细胞粘附过程中跨越单个粘附键的力。应用力探针我以前开发的，我们将研究在滚动粘附级联分子力事件的功能方面。应用DNA纳米技术，我们将继续推进和创造新的分子力探针来检测分子粘附事件的各个方面。了解分子作用力如何影响细胞粘附和信号传导，将为控制细胞行为开辟新的方向，超越传统的生化手段，实现新的细胞筛选技术。拟议的基础设施所支持的研究将创造基础知识和应用技术，这将潜在地造福加拿大的卫生保健系统、生物技术和制药工业。

My research program aims to understand how physical forces regulate cell behaviour. Mechanical forces were recently discovered to play a vital role in the development and functioning of biological systems. Therefore, understanding and controlling mechanical forces in the cellular micro-environment provides significant opportunities for discovery and biotechnology development. Cells interact with their environment mainly through adhesion, where adhesion proteins on cell surfaces bind to receptors on other cells or materials in the environment. A particularly important area of cell adhesion research is the rolling adhesion cascade of leukocytes and circulating tumor cells, which are key processes behind inflammatory response and cancer metastasis. Although forces can now be readily measured on the whole cell scales, very little is known about the dynamics of adhesion force at the molecular level. Understanding and measuring molecular forces is one of the major challenges facing mechano-biology. In particular, little quantitative knowledge exists on the rolling adhesion force magnitude, distribution, stoichiometry, activation state, signalling, and cooperative effects at the molecular level. The lack of mechanistic details at the molecular level hinders further advances in understanding and controlling of cell behaviours. My research program aims to develop new techniques to visualize and control forces across single adhesion bonds during cell adhesion. Applying force probes I have previously developed, we will investigate the functional aspects of molecular force events in rolling adhesion cascade. Applying DNA nanotechnology, we will continue to advance and create novel molecular force probes to detect various aspects of molecular adhesion events. Understanding how molecular forces influence cell adhesion and signalling will open new directions in controlling cell behaviour beyond conventional biochemical means, enabling novel cell screening technologies. Research enabled by the proposed infrastructure will create fundamental knowledge and applied technology that will potentially benefit the Canadian health care system, biotechnology, and pharmaceutical industries.