Assistant Professor of Physics, University of Massachusetts
Ph.D.: Memorial University
Cell Mechanics and Cell Biophysics
In order to apply forces and to control its shape, the cell uses a cytoskeleton. Nature has adapted polymers for this purpose, exploiting their intrinsic timescale-dependent mechanical responses, polymerization and depolymerization dynamics, and ability to cross-link into networks reversibly with the aid of accessory proteins. This material that constitutes the cytoskeleton therefore has intriguing mechanical properties, and by studying it we can learn about the design principles of the cell. Moreover, the mechanics of the cell is important indirectly for therapeutic approaches to diseases such as cancer.
One specific cytoskeleton structure, the mitotic spindle, is responsible for alignment and subsequent equal segregation of chromosomes between daughter cells. The positioning and timing of the spindle is coordinated by a collection of different motor proteins that together with the intrinsic polymer dynamics provide the forcing required for this dynamic process. However, the role that these motors play in spindle dynamics is unclear. We use the budding yeast Saccharomyces cerevisiae as our experimental system, and use fluorescence confocal microscopy to observe and analyze the dynamics of the mitotic spindle and chromosomes. My group has developed new image analysis tools to observe these dynamical processes in living cells in 3D space at high spatial and temporal resolution. By genetically perturbing the motors, we investigate the role that each of the motors plays in dynamical events of cell division.
The cell is highly dynamic and heterogeneous. Experiments performed on in vitro systems reconstituted from purified components can be highly controlled and therefore provide the ability to test theories more rigorously than is possible in vivo. We use reconstituted networks of cytoskeletal proteins, and use microrheology to study the mechanical properties of this model cytoskeleton. Our measurements of the elastic storage and viscous loss moduli of a model system comprising microtubules and F-actin has provided novel results that inspired theoretical modeling. We also use this system for the basic issue of validating microrheology.
Cells must not only generate forces to move and divide, they must also be able to react to forces in their environment. This conversion of physical forces into biological responses is known as mechanotransduction. We are investigating the ability of an ion channel protein involved in equilibrating osmotic pressure in bacteria to function as a biological force sensor. We use fluorescence confocal microscopy, fluorescent labelling strategies, image analysis, and microfluidics to investigate the response of the mechanosensitive channel MscL to osmotic stress in living Escherichia coli cells, and how cell-to-cell variation in protein level influences cell fate.
M.L. Kilfoil, P. Lasko and E. Abouheif. 2009. Stochastic variation: from single cells to superorganisms. HFSP Journal, 3: 373-378.
Y. Gao and M.L. Kilfoil. 2009. Intermittent and spatially heterogeneous single-particle dynamics close to colloidal gelation. Physical Review E, 79: 051406.
V. Pelletier, N. Gal, P. Fournier and M.L. Kilfoil. 2009. Microrheology of Microtubule Solutions and Actin-Microtubule Composite Networks., Physical Review Letters, 102: 188303.
Y. Gao and M.L. Kilfoil. 2009. Accurate detection and complete tracking of large populations of features in three dimensions., Optics Express, 17: 4685.
S.W. Kamp and M.L. Kilfoil. 2009. Universal behaviour in the mechanical properties of weakly aggregated colloidal particles., Soft Matter, 5: 2438-2447.
Y. Gao and M.L. Kilfoil. 2007. Direct Imaging of Dynamical Heterogeneities near the Colloid-Gel Transition., Physical Review Letters, 99: 078301.