Fungi use novel ‘Gel’ proteins to heal injuries
Ever admired the spider spinning its web? It works rapidly exuding a liquid which elongates and transforms into a solid thread forming those beautiful structures we often see glistening in the sunshine after a rain. How do they do it? Spiders have silk glands which produce a protein called spidroin. These protein molecules transform into crosslinked β-sheet fibres upon mechanical shear which occurs when the spider pulls and stretches the silk fibers outside from a duct. Similar cases of crosslinked structures form when there is blood clotting in animals upon injury. There is a liquid-to-solid transition whenever there is a mechanical variation in the flow. Pressure-sensitivity is very important in organisms vulnerable to tear-and-shear damage to their tissues and cells. Hence, organisms evolved ways and means to heal tissue injuries.
In multicellular Fungi transport of nutrients occur through hyphae. Hyphae are the long cell filaments which branch and fuse forming mycelium. They look like heavily branched roots. These hyphal filaments are sub-divided into compartments by deposition of septal walls. These walls have pores, sort of tiny doors, through which the protoplasm containing nutrients, small molecules, etc. can flow easily along long lengths of the mycelia. The phyla Ascomycota and Basidiomycota utilize crystalline molecules or protein aggregates to plug these septal pores near an injury-site to stop the hyphae from ‘bleeding’ out. But not all fungal species are capable of doing this.
Dr. Gregory Jedd’s group at the National University of Singapore studied two species from the Mucoromycota (Phycomyces blakesleeanus and the human pathogen Mucor circinelloides) where septal formation does not occur in young hyphae. Instead, the injured spot in the protoplasm is plugged by a gel. They found Gellins (aptly named) proteins responsible for this protoplasmic gelation. There are two types of these proteins: gellinA and gellinB made up of six β-hairpins as seen in NMR structure. When an injury occurs in hyphae, protoplasm oozes out. A rapid-unfolding event occurs during this pressure-driven event and the Gellins form a β-cross-linked network. The group used CRISPR to eliminate both types of gellins from Mucor circinelloides species to show that protoplasm bled out profusely in the absence of the Gellins thus determining their primary role in wound healing. So how is this different from the spider web story?
Turns out in the case of spidroin, the liquid-to-solid transition occurs via tiny liquid-liquid phase-separated droplets. Whereas crosslinked sheets in Mucoromycota species occur directly from soluble Gellins, no transitory phase separation is seen. This is a novel mechanism in cellular chemistry where sudden changes in force lead to a phase transition, a neat way to mitigate disastrous cell constituent leakage. Once again evolution works in beautiful ways. These plugging mechanisms evolved independently across all organisms but display parallel properties. The authors in their publication in Current Biology hint that such findings in the future may help to incorporate this healing property in soft microfluidic robots. A futuristic dreamboat.
