NSF Postdoctoral Fellowship in Biology FY 2022: The Mechanical Engineering of Dendritic Cell Migration

Ha, Byunghang, Stanford CA

Investigators

Abstract

This research will explore the biophysical mechanisms and genetics that influence the movement of cells (called cell migration). The fellow will use dendritic cells as a model for this work. Dendritic cells are immune cells that migrate through tissues as they patrol for foreign pathogens (i.e., bacteria). However, it is poorly understood how the immune cells can squeeze and migrate through tissues which often have spaces hundred to thousand times smaller than the cells themselves. The Fellow will (1) determine how dendritic cells push, pull, and squeeze their way through tissues, (2) investigate how mechanical properties of the tissues impact dendritic cell migration, and (3) discover genes that either promote or suppress the cell migration. These studies will reveal fundamental insights into the immune cell migration and potentially uncover new mechanisms of cell migration. The genes identified as being involved in dendritic cell migration could potentially guide novel immunotherapies. In addition, the Fellow also aims to increase diversity and inclusion by bringing perspectives and tools of mechanical engineering into the fields of biophysics and immunology and mentoring underrepresented students in the academic fields. Tissues and their extracellular matrices can exhibit viscoelasticity, undergoing irreversible deformations in response to mechanical forces. In viscoelastic matrices, cells can generate forces which can induce the matrix to flow and create and expand an opening in a plastic fashion. The research hypothesizes that first, dendritic cells use its nucleus to create exceptional forces that are not found in adherent cells, plastically opening a path to facilitate migration; second, the matrix mechanical properties such as plasticity, stiffness, and adhesivity impact the migration behaviors. Using tunable biomaterials for 3D culture and confocal microscopy, the Fellow will study the cell migration and how varying matrix properties impact the migration. Moreover, considering that dendritic cells exhibit striking differences in their 3D migration compared to typical adherent cells such as epithelial cells, fibroblasts, and cancer cells, the Fellow assumes that there may be critical genes involved in the cell migration that are unknown. The research aims to discover the genes using genome-wide CRISPR screen and microfluidics-based approach for single cell-in-gel encapsulation for a migration assay. The Fellow will benefit from training in mechanobiology and immunology while conducting the studies. This project will also aid in recruitment and retention of historically underrepresented individuals by providing mentorship to undergraduate and graduate students through outreach programs supported by the host institution. 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.