title: Atomic force microscopy: a multifaceted tool to study membrane proteins and their interactions with ligands.
abstract: Membrane proteins are embedded in lipid bilayers and facilitate the communication between the external environment and the interior of the cell. This communication is often mediated by the binding of ligands to the membrane protein. Understanding the nature of the interaction between a ligand and a membrane protein is required to both understand the mechanism of action of these proteins and for the development of novel pharmacological drugs. The highly hydrophobic nature of membrane proteins and the requirement of a lipid bilayer for native function have hampered the structural and molecular characterizations of these proteins under physiologically relevant conditions. Atomic force microscopy offers a solution to studying membrane proteins and their interactions with ligands under physiologically relevant conditions and can provide novel insights about the nature of these critical molecular interactions that facilitate cellular communication. In this review, we provide an overview of the atomic force microscopy technique and discuss its application in the study of a variety of questions related to the interaction between a membrane protein and a ligand. This article is part of a Special Issue entitled: Structural and biophysical characterization of membrane protein-ligand binding.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Whited
authors.forename: Paul S-H
authors.initials: PS
authors.lastname: Park
mesh_terms: D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D018625:Microscopy, Atomic Force / Q000379:methods*; D015335:Molecular Probes; D011485:Protein Binding
chemical_list: D008024:Ligands; D008565:Membrane Proteins; D015335:Molecular Probes
keywords: AFM; DFS; Energy landscape; Force spectroscopy; F–D; G protein-coupled receptor; GPCR; HOPG; ICAM-1; Imaging; LFA-1; LHRH; Molecular interaction; PE40; Protein structure; Pseudomonas aeruginosa exotoxin 40; SMFS; STM; atomic force microscopy; dynamic single-molecule force spectroscopy; force–distance; highly ordered pyrolytic graphite; intercellular adhesion molecule-1; leukocyte function-associated antigen-1; luteinizing hormone-releasing hormone; scanning tunneling microscopy; single-molecule force spectroscopy