Snooping helices: The elastic path finding algorithm of growing hyphae

Abstract

How living organisms utilize physical mechanisms to sense their environments and make informed decisions is an open question at the interface of biology and physics. In filamentous organisms like fungal hyphae, the decisions are taken by their growing tip cells and later imprinted onto the rest of the multi-cellular filament. Here we report on the growth and pathfinding of hyphae from the opportunistic fungal pathogen Candida albicans, whose ability to cross intestinal epithelial layers is associated to severe systemic infections in humans. It has been sporadically reported that C. albicanss hyphae display helical growth inside or on top of agar gels, helicity turning in the latter case into two-dimensional oscillatory shapes. We provide an extended description of oscillatory C. albicans hyphal growth modalities, revealed under various physical confinements thanks to the use of dedicated microfluidic devices and quantitative time-lapse imaging-based analysis. These include sudden sliding events accompanied by curvature switching of the tip portion, resulting in a final oscillatory morphology of the entire filament, and stable curved tips moving against vertical microfluidic channels walls. These behaviors are unified under the formalism of growing squeezed helices, in which the final hyphal curved shapes result from an elastic energy minimization of a spatially confined helical portion at the tip followed by a continuous solidification front. Ultimately, the combination of our experimental results and theoretical framework provide an insight into the penetration strategy of C. albicans hyphae, which is essential for the virulence of this fungal microorganism. Significance StatementProprioception is the integrated sense of self-movement and body position in complex organisms. Here we describe a novel, mechanical form of proprioception driving directional choice making in tip-growing helical organisms. We show that C. albicans hyphae utilize their built-in helicity as an environment-scanning mechanism to explore their surrounding and find target surfaces for invasion. When confined to surfaces, hyphae continue producing in-plane oscillatory shapes that promote further invasive behavior. C. albicans inherent mechanical instabilities regulate the switching of growth direction and their abrupt directional decisions can be understood as elastic bifurcations of squeezed, confined helices.