Micro- and Nano-plastics: from alterations in the biophysical properties of the cellular microenvironment to the H2S signaling pathway

Micro- and nano-plastics (MNPs) are increasingly recognized as emerging environmental stressors with the potential to affect human health through multiple, interconnected molecular and cellular mechanisms. Although substantial evidence has accumulated regarding their biological effects, the contribution of alterations in the biophysical properties of the cellular microenvironment to MNPs-induced toxicity remains comparatively underexplored. This review summarizes current evidence on the effects of MNPs on the mechanical and viscoelastic properties of the cellular microenvironment and discusses their potential impact on mechano-transduction pathways. Changes in extracellular matrix properties, cell mechanics, cytoskeletal organization, and mechanosensitive signaling may represent important mechanisms through which MNPs exposure influences cell fate, metabolism, inflammation, and tissue homeostasis. Particular attention is given to emerging mechanosensitive pathways, including YAP/TAZ-, Wnt/ß catenin- and PIEZO1-dependent signaling, and to the potential interplay between biochemical and biophysical responses to MNPs exposure. Although the bidirectional relationship between MNPs exposure and hydrogen sulfide (H₂S) homeostasis remains poorly understood and requires further investigation, in this review the recent evidences suggesting that endogenous H₂S signaling may represent an additional molecular pathway affected by MNPs are discussed. Given the established cytoprotective and regulatory functions of H₂S in oxidative stress, inflammation, ferroptosis, and metabolic homeostasis, H₂S-releasing compounds may represent a potential strategy to counteract MNPs-induced cellular damage. Integrating biochemical, molecular, and biophysical approaches may provide a more comprehensive understanding of MNPs toxicity and support the development of preventive and therapeutic strategies, alongside efforts to reduce environmental MNPs contamination through sustainable remediation and safer, biodegradable materials. MNPs effects on Mechanosensing and Hydrogen Sulfide signaling