The membrane of a living cell features a plethora of receptor molecules that enable the cell to interact with its external environment. These interactions are often mediated by multivalent binding between numerous receptor molecules and specific ligands. In the case of motile adherent cells, the combined strength of multiple weak bonds allows the cell to remain firmly attached to a surface while retaining the ability to perform locomotion, such as during cell
crawling and pathogen-host invasion.

In this thesis, I investigate the biophysics of motile adherent cells, through the use of synthetic cells and DNA nanotechnology. I first present a passive motility system, in which lipid vesicles adhere to a substrate through receptor-ligand binding; here, the receptors and ligands consist of synthetic DNA linkers. In particular, I focus on the motion of vesicles over surface density gradients of ligands. Experimental data, supported by numerical and theoretical models, shows that vesicles preferentially drift towards regions with higher ligand density, in a simple form of haptotaxis. The haptotactic drift velocity also exhibits correlations with binding strength and vesicle size.

I also present an active motility system, with the aim of improving the motility of adherent vesicles through the incorporation of a burnt-bridges mechanism. Kinetic models are fitted to experimental data to verify the burnt-bridges mechanism and extract key parameters. These findings helped to design subsequent vesicle motility experiments, in which motility was observed to correlate with the rate of bridge burning. Furthermore, the system enables vesicles to remain adhered at lower bridge densities than in the passive system, corresponding to an order-of-magnitude increase in vesicle velocity.

Overall, the findings from this thesis provide insights into the biophysics of multivalent cell adhesion, motility and haptotaxis, along with design rules helpful for the future development of biomimetic motile systems.