Causes and Effects of Friction in Collective Cell Migration

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This project will study how biological cells move in collective groups. This is an essential process in cancer invasion, tissue development, and wound healing. It is known that the motion results from cell-generated forces. However, how the forces balance to create motion is not clear. This gap in knowledge hinders efforts to control the migration, for example in cancer invasion or wound healing. It is currently believed that a friction force balances the forces produced by each cell. However, there is no established way to measure the friction force. This makes the precise relationship between cell-generated forces and collective motion unknown. This project will measure friction and determine what biophysical factors increase or decrease friction. This research will also study how friction affects the distance over which cell-generated forces are transmitted across a group of cells migrating together. These findings will offer a new way to predict how cell forces bring about the collective migration. This will be the first step to controlling the migration for applications in improving human health. This work will support interdisciplinary training of both graduate and undergraduate students. It will also partner with a Research Experience for Teachers program that will enable a high school teacher to develop hands-on activities that apply topics of this research in the classroom, which will give countless high school students an opportunity to learn about new applications of physics and biology.This research will advance the field by designing experimental methods to measure friction and identifying the biophysical factors controlling friction. To this end, friction will be quantified both at the cell-substrate and cell-cell interfaces through a combination of well-controlled experiments and rigorous measurement of cell tractions, stresses, and velocities. The underlying causes of friction at the cell-substrate and cell-cell interfaces will be systematically studied by perturbing substrate stiffness, cell-substrate adhesions, cell-cell adhesions, and actomyosin contractility. Additionally, theoretical modeling predicts that the ratio of friction at the cell-cell and cell-substrate interfaces sets a length scale controlling the size of a collectively moving group of cells. The research will quantify this length scale in response to various perturbations, hence giving insight into a physics-based mechanism whereby each cell, by altering friction, can affect the collective motion on a length scale larger than itself--the scale of the collective group. Identifying mechanisms such as this one that bridge length scales is essential for understanding complicated, multi-body systems such as collective cell migration.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.