Emergent Collective Guidance of Cancer Cells in Microstructured Environments

Collective cell migration underpins development, wound repair and cancer invasion. In these settings, cells move through extracellular environments that often contain aligned features, for example collagen fibres surrounding tumours. How cells combine these structural cues with biochemical signalling and force generation is still unclear. This project will engineer programmable microenvironments using micropatterned hydrogels and reconfigurable wrinkled substrates to reveal how cancer cells detect and respond to these cues. We will combine Traction Force Microscopy with machine-learning based force inference to quantify subcellular forces on non-planar substrates, and we will use optogenetic Rac1 to locally induce migratory behaviour. Together with molecular analysis of lamellipodial signalling, this approach will uncover how mechanical and biochemical pathways shape collective motion. The outcome will be a quantitative framework for reproducibly assessing how cells interpret aligned microenvironments in tissue-like settings, to understand collective tumour invasion as an integrated response to intracellular signalling and external architectural cues.