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

Abstract Trypanosoma brucei (T. brucei) is a protozoan parasite that lives extracellularly in the body fluids of its hosts. In mammals, these environments include the vascular system and the interstitial spaces of various organs, such as the skin and adipose tissue. 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 than these classical model systems. 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. It can do so in the mammalian host with only one main morphotype. 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.