Measurement and mechanistic modelling of 3D cell migration
Cells moving in 3D display migration modes not observed in 2D. This project will combine live cell imaging and mechanistic modelling to find the physical factors driving the selection of migration modes in 3D.
Many cells in the human body migrate to perform their function. Immune cells move through the body to fight infections and control intruders. Cancer cells move and spread cancer. Stem cells move to damaged tissue, differentiate and build new tissue. Understanding cell migration is fundamentally important and essential for identifying targets for novel therapies.
Most of our knowledge about cell migration comes from experiments in 2 dimensional (2D) cell culture dishes. Cells cultured in 3D extracellular matrices (ECM), however have several different migration modes which are not observed in 2D.
It is therefore important and timely to study cell migration in 3D environment. Our approach is to combine in vitro cell imaging experiments and mathematical modelling to determine the key physical factors driving the selection of migration modes study some aspects of cell migration in 3D. combining
The project will combine:
- an agent-based model using a node-spring network model to represent both the 3D ECM, actin-myosin cytoskeleton network and the cell membrane.
- microfluidic devices with embedded biomimetic hydrogel (3D ECM) to accurately control fluids and ECM deformation while allowing high resolution imaging in 45D(XYZ lambda and t).
- detailed control of hydrogel elasticity (mesh size and crosslink density), degree of protolytic cleavage, density of adhesive sites and fluorescent markers for deformation analysis.
- state of the art fluorescence live cell super-resolution microscopy (Airyscan and iSIM), phase contrast microscopy and quantitative image analysis.
- The candidate must be motivated to develop both experimental and numerical tools for the project and have BSc level in physics or mathematics.
- Candidates with documented experience in scientific programming, machine learning, live cell imaging and microfluidics will be prioritized.
Call 1: Project start autumn 2021
This project is in call 1, starting autumn 2021. Read about how to apply