title: Lipid lateral organization in fluid interfaces controls the rate of colipase association.
abstract: Colipase, a cofactor of pancreatic triacylglycerol lipase, binds to surfaces of lipolysis reactants, like fatty acid and diacylglycerol, but not to the nonsubstrate phosphatidylcholine. The initial rate of colipase binding to fluid, single-phase lipid monolayers was used to characterize the interfacial requirements for its adsorption. Colipase adsorption rates to phosphatidylcholine/reactant mixed monolayers depended strongly on lipid composition and packing. Paradoxically, reactants lowered colipase adsorption rates only if phosphatidylcholine was present. This suggests that interactions between phosphatidylcholine and reactants create dynamic complexes that impede colipase adsorption. Complex formation was independently verified by physical measurements. Colipase binding rate depends nonlinearly on the two-dimensional concentration of phosphatidylcholine. This suggests that binding is initiated by a cluster of nonexcluded surface sites smaller than the area occupied by a bound colipase. Binding rates are mathematically consistent with this mechanism. Moreover, for each phosphatidylcholine-reactant pair, the complex area obtained from the analysis of binding rates agrees well with the independently measured collapse area of the complex. The dynamic complexes between phosphatidylcholine and lipids, like diacylglycerols, exist independently of the presence of colipase. Thus, our results suggest that lipid complexes may regulate the fluxes of other proteins to membranes during, for example, lipid-mediated signaling events in cells.
authors.affiliation: Mt. Sinai School of Medicine, Department of Biomathematical Science, New York, New York 10029, USA.
authors.forename: I P
authors.initials: IP
authors.lastname: Sugar
authors.forename: N K
authors.initials: NK
authors.lastname: Mizuno
authors.forename: M M
authors.initials: MM
authors.lastname: Momsen
authors.forename: H L
authors.initials: HL
authors.lastname: Brockman
mesh_terms: D000327:Adsorption; D000818:Animals; D016000:Cluster Analysis; D003089:Colipases / Q000737:chemistry*; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D015233:Models, Statistical; D010179:Pancreas / Q000201:enzymology; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D011312:Pressure; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D003089:Colipases; D008055:Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; C027891:1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine