Inhalable microplastics of different shapes disrupt airway epithelial homeostasis: A comparative study of fibers and irregular particles

Microplastics are ubiquitously present in the atmospheric environment, with a notably high prevalence of fibrous variants that pose significant inhalation risks. Although extensive research has been conducted on the interaction between spherical microplastics and both cellular systems and animal models, the pulmonary toxicity and biological impact of fibrous microplastics remain poorly understood. The comparative toxicological profiles and mechanistic pathways of two morphologically distinct inhalable microplastics - irregular and fibrous structures - were systematically elucidated through integrated multi-level investigations combining in vivo animal exposure systems and in vitro cell culture models. As a result, restricted ventilatory dysfunction and airway remodeling were observed in both irregular microplastics and fibrous microplastics-treated mice. The exposure of microplastics caused epithelial-mesenchymal transition in airway epithelial cells, characterizing in increased migration rate, decreased cell adhesion and cytoskeleton rearrangement. Based on these toxic effects, fibrous microplastic resulted in more severe airway toxicity than irregular variant did. Most importantly, the exposure of fibrous microplastics increased cilia formation and can be reduced by a Piezo1 inhibitor, of which a unique mechanism that is absent with irregular microplastics. In summary, our study demonstrates that microplastic shape not only modulates toxicological potency but may also influence underlying biological mechanisms, highlighting the imperative to incorporate shape-dependent effects into comprehensive health risk assessments of microplastic pollution.