hamlet interacts with lipid membranes and perturbs their structure and integrity哈姆雷特与脂质膜和扰乱他们的结构和完整性.pdfVIP

HAMLET Interacts with Lipid Membranes and Perturbs Their Structure and Integrity 1. 2. 3. 3 2 Ann-Kristin Mossberg , Maja Puchades , Øyvind Halskau , Anne Baumann , Ingela Lanekoff , Yinxia 4 3 1,4 2 Chao , Aurora Martinez , Catharina Svanborg *, Roger Karlsson 1 Section of Microbiology, Immunology, and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden, 2 Department of Chemistry, University of ¨ Gothenburg, Goteborg, Sweden, 3 Department of Biomedicine, University of Bergen, Bergen, Norway, 4 Singapore Immunology Network, A*STAR, Singapore, Singapore Abstract Background: Cell membrane interactions rely on lipid bilayer constituents and molecules inserted within the membrane, including specific receptors. HAMLET (human a-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded a-lactalbumin (HLA) and oleic acid that is internalized by tumor cells, suggesting that interactions with the phospholipid bilayer and/or specific receptors may be essential for the tumoricidal effect. This study examined whether HAMLET interacts with artificial membranes and alters membrane structure. Methodology/Principal Findings: We show by surface plasmon resonance that HAMLET binds with high affinity to surface adherent, unilamellar vesicles of lipids with varying acyl chain composition and net charge. Fluorescence imaging revealed that HAMLET accumulates in membranes of vesicles and perturbs their structure, resulting in increased membrane fluidity. Furthermore, HAMLET disrupted membrane integrity at neutral