Chemotactic crawling of multivalent vesicles along ligand-density gradients

Abstract: Living cells are capable of interacting with their environments in a variety of ways, including cell signalling, adhesion, and directed motion. These behaviours are often mediated by receptor molecules embedded in the cell membrane, which bind specific ligands. Adhesion mediated by a large number of weakly binding moieties - multivalent binding - is prevalent in a range of active cellular processes, such as cell crawling and pathogen-host invasion. In these circumstances, motion is often caused by gradients in ligand density, which constitutes a simple example of chemotaxis. To unravel the biophysics of chemotactic multivalent adhesion, we have designed an experimental system in which artificial cell models based on lipid vesicles adhere to a substrate through multivalent interactions, and perform chemotactic motion towards higher ligand concentrations. Adhesion occurs via vesicle-anchored receptors and substrate-anchored ligands, both consisting of synthetic DNA linkers that allow precise control over binding strength. Experimental data, rationalised through numerical and theoretical models, reveal that motion directionality is correlated to both binding strength and vesicle size. Besides providing insights into the biophysics of chemotactic multivalent adhesion, our results highlight design rules applicable to the development of biomimetic motile systems for synthetic biology and therapeutic applications.