title: Physiochemical Properties of Aluminum Adjuvants Elicit Differing Reorganization of Phospholipid Domains in Model Membranes.
abstract: Most vaccines contain aluminum adjuvants; however, their exact mechanism of action remains unclear. A novel mechanism by Shi and colleagues proposes aluminum adjuvants may enhance immune activation by binding and reorganizing lipids that are key components of lipid rafts. To better understand the specificity of interaction between aluminum adjuvants and the cell membrane lipids, we present a biophysical study of lipid domain clustering in simple model phospholipid monolayers containing dipalmitoyl-phosphatidylcholine (DPPC) and dioleoyl-phosphatidylcholine (DOPC) exposed to two aluminum adjuvants, Alhydrogel and Adju-Phos. Surface pressure measurements and fluorescence microscopy images verified aluminum adjuvant-induced increase in lipid domain size, even in the key lipid raft components. Additionally, adjuvant induced lipid clustering differed based on the physicochemical properties of the adjuvants. Alhydrogel appeared to reduce monolayer compressibility and insert into the monolayer, while Adju-Phos induced more significant changes in domain size, without compromising the integrity of the monolayer. The Alhydrogel and Adju-Phos-mediated reorganization of phospholipid domains reported here supports the new mechanistic paradigm proposed by Shi and co-workers, and further suggests that lipid clustering is induced even in simple phospholipid membranes. The results present the basis for future exploration into lipid-mediated mechanisms of action for adjuvants.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas 66047, United States.
authors.forename: Lorena R
authors.initials: LR
authors.lastname: Antúnez
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Kansas , Lawrence, Kansas 66045, United States.
authors.forename: Andrea
authors.initials: A
authors.lastname: Livingston
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas 66047, United States.|Department of Chemical and Petroleum Engineering, University of Kansas , Lawrence, Kansas 66045, United States.
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Kansas , Lawrence, Kansas 66045, United States.
authors.forename: Prajnaparamita
authors.initials: P
authors.lastname: Dhar
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000276:Adjuvants, Immunologic / Q000737:chemistry; D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D000535:Aluminum / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D015060:1,2-Dipalmitoylphosphatidylcholine; D000535:Aluminum; C017251:1,2-oleoylphosphatidylcholine
keywords: aluminum adjuvants; interaction; lipids; mechanism of action; organization