Imaging and Controlling Molecular Forces in Live Cell

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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.