CAREER: Biomechanics of Leader Cells

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).

This Faculty Early Career Development (CAREER) award will support research to investigate the migration of groups of cells, specifically, how mechanical forces from the external environment and cellular mechanical forces guide migration. The migration of groups of cells is necessary for development of many tissues. However, migration can also be a sign of development abnormalities or disease advancement.

For cells to move together, a unique sub-set of cells, those called the leader cells, must move to the front. The leader cells receive signals from their surroundings and send signals to other cells in the group so they can all move together. However, how leader cells are uniquely able to carry out these functions is still largely unknown.

This research will begin to unravel how leader cells sense, interpret, and send mechanical signals. This will provide a more comprehensive understanding of how groups of cells move together. This research will be complemented by an educational program to recruit and retain diverse populations of students in STEM.

Underrepresented minorities, women, and first-generation students will be engaged through research, mentoring, and course development for high school, undergraduate and graduate students. Work will also be conducted with K-12 teachers in Virginia using inquiry-based science lessons. The activities will promote STEM awareness to K-12 students using hands-on experiments based on research findings.

The specific goal of this research is to understand how leader cells, biomechanical extracellular matrix (ECM) cues, and cellular mechanics are intertwined to influence the migration of clusters of cells in a process known as collective migration. The central hypothesis is that leader cells polarize to the leading edge through increased protrusive adhesions biased in the direction of the biomechanical cue, interstitial fluid flow, and cellular generated forces required to sustain directed collective migration.

Using a novel, in vitro, 3D microphysiological system that can replicate dynamic ECM cues and incorporate cell clusters to model and induce collective migration, this research will investigate: 1) how leader cells polarize from within a collective unit to the front in the direction of interstitial fluid flow, and 2) if leader cells are mechanically connected and how mechanical forces between leader cells initiate and sustain collective migration. Understanding how leader cells function and lead to collective migration will not only expand our understanding of collective migration driven developmental processes, but also provide a new perspective for therapy design addressing development abnormalities or disease progression where leader cell driven collective migration has gone awry.

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.