title: Multivalent ligand-receptor binding on supported lipid bilayers.
abstract: Fluid supported lipid bilayers provide an excellent platform for studying multivalent protein-ligand interactions because the two-dimensional fluidity of the membrane allows for lateral rearrangement of ligands in order to optimize binding. Our laboratory has combined supported lipid bilayer-coated microfluidic platforms with total internal reflection fluorescence microscopy (TIRFM) to obtain equilibrium dissociation constant (K(D)) data for these systems. This high throughput, on-chip approach provides highly accurate thermodynamic information about multivalent binding events while requiring only very small sample volumes. Herein, we review some of the most salient findings from these studies. In particular, increasing ligand density on the membrane surface can provide a modest enhancement or attenuation of ligand-receptor binding depending upon whether the surface ligands interact strongly with each other. Such effects, however, lead to little more than one order of magnitude change in the apparent K(D) values. On the other hand, the lipophilicity and presentation of lipid bilayer-conjugated ligands can have a much greater impact. Indeed, changing the way a particular ligand is conjugated to the membrane can alter the apparent K(D) value by at least three orders of magnitude. Such a result speaks strongly to the role of ligand availability for multivalent ligand-receptor binding.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, 77843-3012, USA.
authors.forename: Hyunsook
authors.initials: H
authors.lastname: Jung
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Robison
authors.forename: Paul S
authors.initials: PS
authors.lastname: Cremer
mesh_terms: D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D046210:Microfluidic Analytical Techniques; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D011485:Protein Binding
chemical_list: D008024:Ligands; D008051:Lipid Bilayers; D008565:Membrane Proteins