Trypanosomes Modulation of Motility from Swimming to Threading Propulsion in Confined Environments

Trypanosoma brucei is a protozoan parasite that lives extracellularly in all body fluids of its hosts. How the parasite disseminates within the host remains largely unresolved. It is clear however, that parasite motility plays a central role. The unicellular, eukaryotic flagellate is a versatile microswimmer, like bacteria or sperm cells, albeit structurally far more complex. In addition to possessing a flagellum attached alongside a strongly polarised cell body, the parasite is capable of swimming both forwards and backwards. The trypanosome must be capable of navigating effectively even under extreme physical and mechanical constraints. This means that the cell is mechanically adapted to motion in diverse challenging microenvironments. To address how, we study the parasites in different viscoelastic regimes up to conditions mimicking tissue confinement. Next to quantitative high speed video microscopy, we employ digital holography microscopy, yielding three-dimensional subcellular resolution. We detail the mechanical reaction of the flexible cell body with its uniquely attached flagellum to increasing confinement and show how the trypanosomes are able to maintain their motile capabilities to spread in dense tissue.