Cellular Integration of Physical Cues in the Microenvironment

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In the body, our cells are constantly subjected to mechanical forces arising from many sources. This can include the expansion of our lungs, the beating of our heart, our blood flow and the contraction of our muscles as we move. Furthermore, the mechanical properties of our organs and tissues (such as stiffness) can have a profound effect on the functioning and development of our bodies. The mechanical stiffness of the cellular environment influences many diverse processes in the body, such as stem cell fate, cell growth and death, the formation of new muscle tissue and even the spread of cancer or the progression of heart disease. Importantly, in the body, cells can be simultaneously exposed to rapid changes in stiffness as well as the effects of compression and stretch. Although it has become well appreciated that cells are sensitive to mechanical cues in their local environment, the exact mechanisms cells use to sense and respond to physical information remain poorly understood. However, because these sensing abilities are so crucial our development, growth and well being, it is imperative to understand how they operate. In this research program, we will delve into the physical and molecular mechanisms that govern the ability of a cell to sense and respond to mechanical cues in its environment. Utilizing state of the art biophysical and genetic approaches we will develop a mechanistic understanding of the earliest response of a cell to physical forces in real time. We have also developed techniques that will allow us to examine how cells respond to the simultaneous exposure to deformation and changes in the stiffness of their environment. Employing highly interdisciplinary life and physical science training and methodologies, we will be able to address these fundamental questions in cell biology. Exploiting the sensitivity of cells to physical forces and mechanical properties has already been proposed as means to control stem cell fate or precondition therapeutic cells for transplantation. Alternatively, measuring changes in the physical properties of cells is thought to be a viable means of detecting cancerous cells in the body and bloodstream. Therefore, enhancing our fundamental knowledge about the mechanical aspects of cell biology has the potential to direct the development of future medical detection and treatments of disease. Importantly, the Pelling Lab, at the University of Ottawa, has already contributed fundamental new knowledge that has found potential applications in some of these areas. The new knowledge generated by the Pelling Lab may impact Canadians through the development of next generation healthcare detection and treatment technologies. This research program will train the next generation of Canadian highly qualified personnel (HQP) to develop exciting and revolutionary new knowledge with many potential applications. HQP will receive training in advanced cell/molecular biology, advanced microscopy, quantitative analysis, computer programming, 3D printing, microfabrication, device design, construction and prototyping. HQP will work and collaborate within an interdisciplinary laboratory, gaining highly transferable skills for later careers in academia or industry. HQP who are fluent in the languages of biology and physics are central to the objectives of this research program as well as any eventual downstream applications of this work. HQP who have been trained in the Pelling Lab have gone on to diverse careers that have directly impacted Canada's knowledge based economy in the energy, automobile, healthcare and bioscience industries.