Mac-chanosensing: an in vivo study of how substrate stiffness regulates macropinocytosis during macrophage migration

Macropinocytosis is a process cells use to take in liquid from the outer environment. This process helps phagocytic cells of the immune system recognise potential infections but can also be rewired to fuel tumour growth. Evidence from cells grown in a dish (in vitro) suggests that apart from chemical signals, the physical properties of the surrounding environments can affect how macropinocytosis is regulated. However, data from cells in a living organism (in vivo) are still lacking. I aim to investigate this by modulating the physical properties of tissues surrounding macrophages in frog (Xenopus) embryos using mechanical and optical techniques. I will also perform detailed high-resolution microscopy analyses of macrophage migration, the morphology of macropinocytosis and the removal of bacteria in a second model organism, the transparent zebrafish larvae. Given the importance of macropinocytosis in pathophysiological conditions, this study represents a critical step towards understanding how physical cues affect cellular behaviours.