Cell division is essential for life; it underlies the development of humans from embryo to full-grown adult, as well as regenerative processes such as wound healing and pathologies such as cancer. While cell division is an inherently mechanical process, its physical nature is poorly understood. This fundamental research will use a device called an "atomic force microscope" (AFM) to measure the small forces created by a cell and the stiffness changes of the cell during division into two cells. In addition, the AFM will be used to measure how the division of cells is changed by application of force. As cell division is an essential process in biology, the results of this work will contribute to understanding development and growth of organisms, tissue development, tissue regeneration, and cancer. The interdisciplinary approach taken in this research, involving the application of cutting edge techniques in engineering to the study of cell biology, will have a positive impact on the education of engineers and biologists including those from underrepresented groups. In addition, the novel measurement device built during the project will remain as a resource for future research by the current team and their colleagues.
In tissues, cell division is physically restricted in all dimensions by neighboring cells and extracellular matrix. Dividing cells must be able to generate significant forces in a spatially and temporally coordinated manner to create the morphological changes accompanying cell division, and in some contexts must do this while experiencing physiological forces. How cells generate and respond to such forces remains unclear, as cell division has been primarily studied in cells cultured on flat petri dish surfaces. The objective of this project is to elucidate how cells generate and respond to forces, and alter their structural properties, during cell division. We will construct and use a high-resolution side-view imaging atomic force microscope to directly measure forces generated by cells during each stage of cell division while simultaneously imaging the dynamic cytoskeletal and chromosomal rearrangements in dividing cells in epi-fluorescence along a plane perpendicular to the sample surface. With this tool, we aim to address the following important questions regarding the mechanics of cell division: (1) What are the forces generated by cells following during cell division and how are they generated?; (2) How do the viscoelastic properties of cells change during each stage of cell division?; and finally (3) what is the effect of applied force on cell division?
