title: Activation of integrin function by nanopatterned adhesive interfaces.
abstract: To study the function behind the molecular arrangement of single integrins in cell adhesion, we designed a hexagonally close-packed rigid template of cell-adhesive gold nanodots coated with cyclic RGDfK peptide by using block-copolymer micelle nanolithography. The diameter of the adhesive dots is < 8 nm, which allows the binding of one integrin per dot. These dots are positioned with high precision at 28, 58, 73, and 85 nm spacing at interfaces. A separation of > or = 73 nm between the adhesive dots results in limited cell attachment and spreading, and dramatically reduces the formation of focal adhesion and actin stress fibers. We attribute these cellular responses to restricted integrin clustering rather than insufficient number of ligand molecules in the cell-matrix interface since "micro-nanopatterned" substrates consisting of alternating fields with dense and no nanodots do support cell adhesion. We propose that the range between 58-73 nm is a universal length scale for integrin clustering and activation, since these properties are shared by a variety of cultured cells.
authors.affiliation: University of Heidelberg, Institute for Physical Chemistry, Biophysical Chemistry, INF 253, 69120 Heidelberg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Arnold
authors.forename: Elisabetta Ada
authors.initials: EA
authors.lastname: Cavalcanti-Adam
authors.forename: Roman
authors.initials: R
authors.lastname: Glass
authors.forename: Jacques
authors.initials: J
authors.lastname: Blümmel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eck
authors.forename: Martin
authors.initials: M
authors.lastname: Kantlehner
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Spatz
mesh_terms: D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D005353:Fibronectins / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D016023:Integrins / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008823:Micelles; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods*; D010455:Peptides / Q000737:chemistry; D022502:Stress Fibers / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D005353:Fibronectins; D016023:Integrins; D008024:Ligands; D008823:Micelles; D010455:Peptides; D006046:Gold