Abstract: The forces cells apply to their surroundings control biological processes such as growth, adhesion, development, and migration. Experimental techniques have primarily focused on measuring tractions applied by cells to synthetic two-dimensional substrates, which do not mimic in vivo conditions. This talk will describe the development and application of an experimental technique for quantification of cellular forces in a natural three-dimensional matrix. Cells and their surrounding matrix are imaged in three dimensions with confocal microscopy, cell-induced matrix displacements are computed using digital volume correlation, and tractions are quantified directly from the full-field displacement data.
The technique is used to investigate how cells employ physical forces in processes such as division, invasion, and force sensing. During division, a single mother cell undergoes a drastic morphological change to split into two daughter cells. In a three-dimensional matrix, dividing cells apply tensile force to the matrix through thin, persistent extensions that in turn direct the orientation and location of the daughter cells. Invading cells extend thin protrusions into the matrix and anchor themselves to the matrix using these protrusions. This observation is consistent with models that predict invading cells apply tension to these anchor points to extend further into the matrix. Finally, a mechanics model is developed to estimate a critical spacing under which cells can sense the displacements induced in the matrix by their neighbors. The application of this model to investigate a cell’s ability to sense force is further discussed.
Bio: Jacob Notbohm’s research focuses on applying principles of mechanics of materials and applied mathematics to understand how physical interactions between cells and their three-dimensional surroundings control cellular processes such as migration, division, adhesion, and invasion. To conduct this interdisciplinary research, Jacob has utilized a range of experimental and theoretical tools such as confocal microscopy, digital image correlation, atomic force microscopy, micropipette aspiration, magnetic tweezers, and simple analytical and finite element models. Jacob is currently a PhD Candidate in Mechanical Engineering at the California Institute of Technology where he is supported by an NSF Graduate Research Fellowship. Jacob received his BS from the University of Wisconsin in Engineering Mechanics in 2007 and MS from the California Institute of Technology in Mechanical Engineering in 2009.