title: Nanopatterned polymer substrates promote endothelial proliferation by initiation of β-catenin transcriptional signaling.
abstract: Control of endothelial phenotype involves a variety of signaling pathways and transcriptional regulators, including the junctional protein β-catenin. This multifunctional signaling molecule is part of adhesion contacts in the endothelium and is able to translocate into the nucleus to activate genetic programs and control proliferation and the fate of the cells. We investigated the influence of laser-generated nanopatterns on polymeric cell culture substrates on endothelial tissue architecture, proliferation and β-catenin signaling. For our experiments human microvascular endothelial cells or CD34(+) endothelial progenitor cells, isolated from human adipose tissue, were cultured on polyethylene terephthalate (PET) substrates with oriented nanostructures with lateral periodicities of 1.5 μm and 300 nm, respectively. The surface topography and chemistry of the PET substrates were characterized by electron microscopy, atomic force microscopy, water contact angle measurement and X-ray photoelectron spectroscopy. Analysis of cell phenotype markers as well as β-catenin signaling revealed that short-term culture of endothelial cells on nanostructured substrates generates a proliferative cell phenotype associated with nuclear accumulation of β-catenin and activation of specific β-catenin target genes. The effects of the nanostructures were not directly correlated with nanostructure-induced alignment of cells and were also clearly distinguishable from the effects of altered PET surface chemistry due to photomodification. In summary, we present a novel mechanism of surface topology-dependent control of transcriptional programs in mature endothelium and endothelial progenitor cells.
authors.affiliation: Department of Pharmacology and Toxicology, University of Graz, A-8010 Graz, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schernthaner
authors.forename: Bettina
authors.initials: B
authors.lastname: Reisinger
authors.forename: Heimo
authors.initials: H
authors.lastname: Wolinski
authors.forename: Sepp D
authors.initials: SD
authors.lastname: Kohlwein
authors.forename: Ameli
authors.initials: A
authors.lastname: Trantina-Yates
authors.forename: Marc
authors.initials: M
authors.lastname: Fahrner
authors.forename: Christoph
authors.initials: C
authors.lastname: Romanin
authors.forename: Haybat
authors.initials: H
authors.lastname: Itani
authors.forename: David
authors.initials: D
authors.lastname: Stifter
authors.forename: Gerd
authors.initials: G
authors.lastname: Leitinger
authors.forename: Klaus
authors.initials: K
authors.lastname: Groschner
authors.forename: Johannes
authors.initials: J
authors.lastname: Heitz
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D018625:Microscopy, Atomic Force; D055806:Microvessels / Q000166:cytology; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D056951:Photoelectron Spectroscopy; D011093:Polyethylene Terephthalates / Q000737:chemistry / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*; D014867:Water / Q000737:chemistry; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D011093:Polyethylene Terephthalates; D051176:beta Catenin; D014867:Water; D019938:Cyclin D1