title: Binding of Vinculin to Lipid Membranes in Its Inhibited and Activated States.
abstract: Phosphoinositols are an important class of phospholipids that are involved in a myriad of cellular processes, from cell signaling to motility and adhesion. Vinculin (Vn) is a major adaptor protein that regulates focal adhesions in conjunction with PIP2in lipid membranes and other cytoskeletal components. The binding and unbinding transitions of Vn at the membrane interface are an important link to understanding the coordination of cell signaling and motility. Using different biophysical tools, including atomic force microscopy combined with confocal fluorescence microscopy and Fourier transform infrared spectroscopy, we studied the nanoscopic interactions of activated and autoinhibited states of Vn with lipid membranes. We hypothesize that a weak interaction occurs between Vn and lipid membranes, which leads to binding of autoinhibited Vn to supported lipid bilayers, and to unbinding in freestanding lipid vesicles. Likely driving forces may include tethering of the C-terminus to the lipid membrane, as well as hydrophobic helix-membrane interactions. Conversely, activated Vn binds strongly to membranes through specific interactions with clusters of PIP2embedded in lipid membranes. Activated Vn harbored on PIP2clusters may form small oligomeric interaction platforms for further interaction partners, which is necessary for the proper function of focal adhesion points.
authors.affiliation: Physical Chemistry I, Biophysical Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany. Electronic address: mridulavd@gmail.com.
authors.forename: Mridula
authors.initials: M
authors.lastname: Dwivedi
authors.affiliation: Physical Chemistry I, Biophysical Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany. Electronic address: roland.winter@tu-dortmund.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Winter
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D053835:Unilamellar Liposomes / Q000737:chemistry*; D016596:Vinculin / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010743:Phospholipids; D053835:Unilamellar Liposomes; D016596:Vinculin