Tetrabromobisphenol A, but not bisphenol A, disrupts plasma membrane homeostasis in myeloid cell models - A novel threat from an established persistent organic pollutant.

Bisphenol A (BPA, a plastic polymer component) and tetrabromobisphenol A (TBBPA, a brominated flame retardant) are industrial compounds and representative persistent organic pollutants (POPs) with similar chemical structure. We studied their impact on biological membrane dynamics, which is an emerging and understudied target for environmental contaminants, using a set of state-of-the-art methods. We found that exposure to TBBPA, but not to BPA, leads to disruption of biophysical homeostasis of the plasma membrane in myeloid cell lines HL-60, THP-1 and Mono Mac 6. Applied methods include: pyrene excimer formation, fluorescence anisotropy, solvatochromic shift ratiometry (using di-4-ANEPPDHQ, NR12A and laurdan) and fluorescence recovery after photobleaching. TBBPA increased rotational and lateral mobility and decreased general polarity and lipid order in plasma membranes of myeloid cells, but decreased mobility and increased rigidity in internal membranes of the same cells. Strikingly, BPA had no significant membrane effects in these cells, suggesting a specific molecular interaction mechanism of TBBPA action which may potentially lead to disruption of immune function. Identification of this novel threat from an established pollutant with documented exposure pathways highlights the possibility that immunotoxicity of POPs may contribute to their environmental toxicity burden.