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Dynamics of cell invasion in three dimensions

Jacob Notbohm (Caltech), Ayelet Lesman (), David Tirrell (), G. Ravichandran (Caltech)

Mechanics and Physics of Biological Cells

Tue 2:40 - 4:00

Barus-Holley 141

The forces cells apply to their surroundings control biological processes such as growth, adhesion, development, and migration. Experimental techniques to measure such forces have primarily focused on measuring tractions applied by cells to synthetic two-dimensional substrates, which do not mimic in vivo conditions for most cell types. 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 cell spreading, a model system for cell invasion and migration in three dimensions. When encapsulated in a fibrous matrix, initially spherical cells begin to spread within hours. By imaging cell spreading in real time, physical forces during spreading are quantified in three dimensions. Spreading cells extend thin protrusions into the matrix and anchor themselves to the matrix using these protrusions. They apply tension to these anchor points to extend further into the matrix, consistent with observations from previous work that imaged matrix fibers during cell invasion to observe fiber reorientation and degradation.