Nanoplastics remodel the extracellular matrix mechanical microenvironment to activate hepatic stellate cells

Abstract

Nanoplastics, an emerging class of environmental contaminants, have become a growing concern due to their widespread distribution and potential to interfere with cellular and tissue homeostasis. The liver, as a primary site of xenobiotic metabolism and clearance, is particularly vulnerable to nanoplastic exposure. Hepatic stellate cells (HSCs) play a central role in maintaining liver extracellular matrix (ECM) homeostasis and in initiating fibrogenic responses; therefore, understanding how nanoplastics affect HSC behavior is critical for elucidating early mechanisms of nanoplastic-induced liver injury. To achieve physiologically relevant modeling, we employed HSC and collagen hydrolysate to construct a simplified matrix–cell–matrix mimicking the microenvironment of the hepatic space of Disse, we found that both aminated (PS-NH₂) and carboxylated (PS-COOH) polystyrene nanoplastics were retained within collagen hydrolysate matrices and altered their viscoelastic properties, with more significantly negatively charged PS-COOH increasing matrix viscosity. HSCs cultured within PS-COOH–treated matrices exhibited enhanced proliferation and migration without apparent cytotoxicity, accompanied by intensified F-actin stress fiber formation and nuclear translocation of the mechanosensitive coactivator yes-associated protein (YAP). Together, these findings indicate that nanoplastics may indirectly activate quiescent HSCs by remodeling ECM mechanical properties, rather than through direct cellular uptake. This work provides a mechanobiological perspective linking environmental nanoplastic exposure to early hepatic fibrogenesis.

Keywords

Nanoplastics / hepatic stellate cells / extracellular matrix / mechanical properties

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