A heart-on-a-chip simultaneously monitoring mechanical and electrophysiologic signals reveals charge-dependent micro/nano plastic cardiotoxicity.

Environmental micro/nano plastics (MNPs) have recently been identified within the human circulation and myocardial tissues, yet the specific biophysical drivers of their toxicity remain poorly defined. While previous models have demonstrated general cardiotoxic effects, they typically utilize single-type particles that fail to account for the diverse surface charges acquired during environmental aging. Here, using a multimodal heart-on-a-chip platform, we show that the cardiotoxicity of polystyrene MNPs is strongly associated with their surface charge, with positive charged particles (pPS-MNPs) producing the most pronounced suppression of electromechanical function. Further, we observed that pPS-MNPs preferentially accumulate within cardiomyocytes and may physically interfere with L-type calcium channels (Cav1.2). This spatial association is consistent with the observed suppression of Ca2+ transients and mitochondrial stress, and suggests a contribution of Cav1.2-associated Ca2+ dysregulation to electromechanical impairment. Our findings, validated in a long-term rat exposure model, identify surface charge as a key determinant of MNP cardiotoxicity and highlight the necessity of charge-specific risk assessments for plastic pollution.