Fungal hyphae through the lens of microfluidic devices: From biological properties to novel therapeutic opportunities.

Fungal diseases are increasingly being recognized as a major health problem worldwide. Advancing therapeutic approaches against fungal pathogens require comprehensive knowledge of their biological properties, which enable fungi to explore host environments, interact with host cells and coinhabiting microorganisms, adopt colonization and infective strategies. Thus, fungus intrinsic as well as extrinsic mechanisms functionally cooperate for successful host infection and disease development. In this regard, fungal hyphae, i.e. long, filamentous structures with polarized tip growth, represent a unique feature of multicellular fungi and play critical roles during the infectious process, calling for in-depth characterization of their functional and structural properties. In this context, reproducing hyphal growth in physiological conditions represents a fundamental prerequisite for disease modeling and therapeutic development. For their potential to accommodate and interconnect cells and miniature tissues, microfluidic devices stand as unique opportunities in this direction by overcoming acknowledged limits of animal models and traditional cell cultures. Based on these premises, we herein provide an overview of the use of microfluidic devices in the study of fungal hyphae, from the investigation of their biological properties to the analysis of inter-organismal networking, including the interaction between fungal hyphae and host cells. By dissecting hyphal strategies of environmental navigation as well as modalities of cell-cell interactions, resorting to microfluidics devices may provide novel opportunities for therapeutic targeting of fungal pathogens, in line with the objectives of the World Health Organization.