Measurement of 3D Cell Dynamics: Forces and Vibrations

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The mechanical behaviour of cells is altered by various diseases such as cancer, arthritis and cardiovascular disease. In particular, dynamic mechanical behaviour provides a key to diagnosing diseases and identifying malignant cells, as it reveals the metabolic state and metastatic ability of a cell. Specifically, the study of the dynamics of cell migration and cell wall vibration form an engineering research program of considerable potential. The proposed research program will develop methods to investigate these dynamic activities and obtain a fundamental understanding of them, with the intent to determine the interplay between them, which will form the basis for integrated diagnostic tools used to identify metastatic diseases.***The first objective is to develop a 3D cell traction force microscopy technology to characterize and quantify the 3D forces and energies induced by 3D cell migration, as an extension of my current NSERC Discovery program. During migration through tissue, the cells must apply forces, known as cell traction forces (CTF), to the surrounding extracellular matrix (ECM). Since CTF is closely related to the metastatic potential of the cells, the quantitative characterization of CTF is essential to diagnosing metastatic diseases. Both 3D CTF and energies induced by cells will be determined by applying digital volume correlation (DVC), developed in the current Discovery program, to the 3D images of ECM affected by 3D cell migration, as a measure of the cell's metastatic properties.***The second objective is to develop the engineering technology to measure the cell wall vibration (CWV) that provides direct insight into a cell's metabolic state. Recently, it was found that cell membranes vibrate in the kilohertz range, which is caused by the cellular metabolism and motor proteins. Since metabolism directly represents the state of health of the cell and metastatic potential, CWV can be adopted as a new measure for the diagnoses of diseases and abnormalities of the cell. However, this method has been applied only to plant cells and not mammalian cells. Extension of this method to mammalian cells will face many critical engineering challenges. My group has had some recent preliminary success with using liquid-cell AFM and is ready to tackle these challenges.***The metastatic potential measured by the CTF will be related to cell metabolism via CWV, which is the long-term intent of this engineering research program. It is hoped that eventually the interplay between cell dynamic behaviour and metastatic properties can be determined and the integrative mechano-biophysical model will be developed.***The outcomes of this research program are crucial to understanding the cellular dynamics involving cancer metastasis, and will thus help eventually develop an efficient diagnostic tool of metastatic cancers and design therapeutic strategies for their suppression.**