Docosahexaenoic acid disrupts lipid raft clustering and enhances proliferation and survival of EL4 lymphomas

Abstract

An emerging molecular mechanism by which docosahexaenoic acid (DHA) acyl chains modify cellular function is through changes in lipid raft organization. Biophysical studies in liposomes show that DHA does not directly modify rafts; instead, it incorporates into non‐rafts to modify the lateral organization of proteins such as the major histocompatibility complex (MHC) class I. Here we tested predictions of the model at a cellular level by incorporating DHA and eicosapentaenoic acid (EPA) into the membranes of EL4 lymphomas. Quantification of fluorescence microscopy images showed that DHA, but not EPA, diminished lipid raft clustering by incorporating into rafts and changed MHC I lateral organization by increasing the fraction of the non‐raft protein into rafts. We next addressed the functional consequences of treating EL4 cells given changes in raft organization are associated with suppression of cellular proliferation. Both EPA and DHA enhanced the proliferation and survival of EL4 cells relative to controls. Taken together, our findings are not in agreement with biophysical studies; therefore, we propose a new model, which reconciles contradictory viewpoints from biophysical and cellular studies, to explain how DHA‐containing phospholipids modify rafts. Furthermore, our data highlight the notion that n‐3 PUFAs exert differential functional effects depending on the cell type.