Electric Field Effect on Phospholipid Monolayers at an Aqueous-Organic Liquid-Liquid Interface

The electric potential difference across cell membranes, known as the membrane potential, plays an important role in the activation of many biological processes. To investigate the effect of the membrane potential on the molecular ordering of lipids within a biomimetic membrane, a self-assembled monolayer of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) lipids at an electrified 1,2-dichloroethane/water interface is studied with X-ray reflectivity and interfacial tension. Measurements over a range of electric potential differences, -150 mV to +130 mV, that encompass the range of typical bio-membrane potentials demonstrate a nearly constant and stable structure whose lipid interfacial density is comparable to that found in other biomimetic membrane systems. Measurements at higher positive potentials, up to 330 mV, illustrate a monotonic decrease in the lipid interfacial density and accompanying variations in the interfacial configuration of the lipid. Molecular dynamics simulations, designed to mimic the experimental conditions, show that the measured changes in lipid configuration are due primarily to the variation in area per lipid with increasing applied electric field. Rotation of the SOPC dipole moment by the torque from the applied electric field appears to be negligible, except at the highest measured potentials. The simulations confirm in atomistic detail the measured potential-dependent characteristics of SOPC monolayers. Our hybrid study sheds light on phospholipid monolayer stability under different membrane potentials, which is important for understanding membrane processes. This study also illustrates the use of X-ray surface scattering to probe the ordering of surfactant monolayers at an electrified aqueous-organic liquid-liquid interface

Additional file 1: of Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions

Figure S1. Risperidone treatment does not affect tumor histopathology or lung metastatic potential. (A) H&E staining of tumor sections. (B) qPCR analysis of lung metastasis and the resulting dot plot analyzed using the Mann-Whitney test. Each dot in this plot represents one mouse. (AI 4884 kb

Additional file 7: of Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions

Figure S7. Effects of ruxolitinib on pSTAT5 and tumor latency. (A) Serum prolactin levels of mice. (B) Immunohistochemistry analysis and the accompanying dot plot for pSTAT5+ cells. The p values were determined using the Mann-Whitney test. Each dot in this plot represents one mouse. (C) Kaplan-Meier tumor-free survival curve of mice infected by RCAS-HRasQ61L. The p value was determined by generalized Gehan-Wilcoxon test with Rho = 1. (AI 6247 kb

Additional file 4: of Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions

Figure S4. Pimozide accelerates the development of early lesions initiated by RCAS-caErbB2 while lowering the anticancer barrier of apoptosis. (A) Immunohistochemical staining for the HA tag on the RCAS-ErbB2 provirus with the corresponding dot plot. (B) Immunofluorescence staining for Ki67 with the accompanying dot plot. (C and D) Immunofluorescence staining for cleaved caspase 3 (C) and TUNEL assay (D) with the accompanying dot plots. The Mann-Whitney test was used to determine the p values. Each dot in these plots represents one mouse. (AI 15221 kb

Additional file 5: of Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions

Figure S5. Effects of aripiprazole and clomipramine on biomarkers and lesion burden. (A) Serum prolactin levels of mice in the aripiprazole study. (B) Lesion burden determined by immunohistochemical staining for the HA tag on RCAS-caErbB2. (C) Ki67+ cells determined by immunofluorescence staining. (D) TUNEL+ cells. (E) Serum prolactin levels of mice in the clomipramine study. (F) Lesion burden determined by immunohistochemical staining for the HA tag on RCAS-caErbB2. The p values were determined using the Mann-Whitney test. Each dot in these plots represents one mouse. (AI 713 kb

Additional file 2: of Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions

Figure S2. Risperidone treatment accelerates early lesion development of MMTV-Wnt1 transgenic mice. (A) Carmine whole mount staining of mammary glands from MMTV-Wnt1 transgenic mice. (B) H&E staining of mammary gland sections of MMTV-Wnt1 mice. (C) pSTAT5 immunohistochemical staining of mammary gland sections of MMTV-Wnt1 mice. (AI 22593 kb

Additional file 6: of Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions

Figure S6. Effects of genetic ablation of STAT5a on downstream factors of STAT5. Immunohistochemistry analysis of β-casein in caErbB2 early lesions. (AI 4570 kb

Additional file 3: of Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions

Figure S3. Pimozide increases serum prolactin levels, pSTAT5 in early lesions, and β-casein, while aripiprazole does not impact pSTAT5. (A) Serum prolactin levels. (B) pSTAT5+ cells determined by immunohistochemistry analysis. (C) Immunohistochemistry analysis of β-casein. (D) pSTAT5+ cells determined by immunohistochemistry analysis. The p values were determined using the Mann-Whitney test. Each dot in these plots represents one mouse. (AI 6764 kb