1. Engineering Approaches for to Control Cell Migration Decisions – Experimental
Mentor: Professor Ian Schneider
During development, wound healing and cancer progression, cells must migrate to particular targets. They do this by sensing aligned fibers of insoluble extracellular matrix (ECM) proteins such as collagen and gradients in ECM stiffness, directing migration through processes of contact guidance and durotaxis, respectively. While both processes have been studied in isolation, how cells integrate this information and make migration decisions is unknown. The goal of this project is to control collagen fiber alignment through self-assembly and stiffness through photopolymerizable hydrogels to create multi-cue environments. These tools will be used in conjunction with fluorescent biosensors and live-cell light microscopy techniques that allow for the visualization of cell migration. Understanding how cells respond to precisely defined structural and mechanical properties will uncover fundamental mechanisms of cancer invasion and metastasis as well as guide the design of tissue engineered constructs for wound healing.
Example REU Project: Dermal fibroblasts will be seeded on aligned collagen fibers transferred to hydrogels with gradients in stiffness. Collagen orientation, local stiffness and cell migration will be assessed in these multi-cue environments. The REU student will learn how to align collagen fibers and make stiffness gradients in hydrogels. The migratory behavior of cells and traction forces exerted by cells will be assessed using microscopy and intracellular proteins will be targeted using RNA interference or gene editing. This project will expose the REU student to collagen alignment techniques, mechanical and structural property measurements, cell biology and quantitative light microscopy.