CAREER: Engineering approaches to control collective cell migration using electrotaxis

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The ability to direct the migration of cells in living tissues could accelerate wound healing or slow the spread of cells in diseases like cancer. Cell movement in the body has been shown to be influenced by local electrochemical fields. This behavior, called electrotaxis, can be directed by the external application of electric fields. Deepening our knowledge of electrotaxis will enable the development of tools to direct cell migration. This project also includes several education initiatives, including a yearly, week-long ‘Science Storytelling’ training workshop to help young scientists learn how to share the stories behind their research with the public. This project combines mechanistic understanding with engineering control. It merges primary skin tissue and new electro-bioreactor technology to establish a connection between native collective cell behaviors and our ability to control them. This should help to better apply electrotaxis as a tool for biotechnology. Aim 1 calls for a comprehensive characterization of how biophysical aspects of a tissue (shape, size, cell-cell adhesion) and electric field strength act as a ‘gas pedal’ affecting our ability to accelerate migration and increase forward tissue motion. Aim 2 defines how electrotaxis physically reprograms key migratory machinery needed for cell migration, with emphasis on determining necessary end-effectors and possible pharmacological ways to target them to improve electrotaxis. Aim 3 characterizes how native cell-cell interactions actually compete with electrotactic control and develops new approaches to mitigate this problem. Together, these aims will deliver fundamental ‘design rules’ for electrotaxis and use these rules to demonstrate how next-generation bioelectric interfaces will enable a fundamentally new way to engineer living tissue.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.