title: Influence of membrane cholesterol and substrate elasticity on endothelial cell spreading behavior.
abstract: Interactions between implanted materials and the surrounding host cells critically affect the fate of bioengineered materials. In this study, the biomechanical response of bovine aortic endothelial cells (BAECs) with different membrane cholesterol levels to polyacrylamide (PA) gels was investigated by measuring cell adhesion and spreading behaviors at varying PA elasticity. The elasticity of gel substrates was manipulated by cross-linker content. Type I collagen (COL1) was coated on PA gel to provide a biologically functional environment for cell spreading. Precise quantitative characterization of changes in cell area and perimeter of cells across two treatments and three bioengineered substrates were determined using a customized software developed for computational image analysis. We found that the initial response of endothelial cells to changes in substrate elasticity was determined by membrane cholesterol levels, and that the extent of endothelial cell spreading increases with membrane cholesterol content. All of the BAECs with different cholesterol levels showed little growth on substrates with elasticity below 20 kPa, but increased spreading at higher substrate elasticity. Cholesterol-depleted cells were consistently smaller than control and cholesterol-enriched cells regardless of substrate elasticity. These observations indicate that membrane cholesterol plays an important role in cell spreading on soft biomimetic materials constructed with appropriate elasticity.
authors.affiliation: Department of Physics and Astronomy, University of Missouri, Columbia, Missouri 65211, USA. kuihong@gmail.com
authors.forename: Zhongkui
authors.initials: Z
authors.lastname: Hong
authors.forename: Ilker
authors.initials: I
authors.lastname: Ersoy
authors.forename: Mingzhai
authors.initials: M
authors.lastname: Sun
authors.forename: Filiz
authors.initials: F
authors.lastname: Bunyak
authors.forename: Paul
authors.initials: P
authors.lastname: Hampel
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Hong
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Li
authors.forename: Irena
authors.initials: I
authors.lastname: Levitan
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Meininger
authors.forename: Kannappan
authors.initials: K
authors.lastname: Palaniappan
mesh_terms: D000180:Acrylic Resins; D000818:Animals; D057005:Bioengineering; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology* / Q000502:physiology; D024042:Collagen Type I; D003432:Cross-Linking Reagents; D004285:Dogs; D004548:Elasticity; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000254:growth & development; D005782:Gels; D008566:Membranes / Q000737:chemistry; D008858:Microscopy, Phase-Contrast; D012984:Software; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D002784:Cholesterol; D024042:Collagen Type I; D003432:Cross-Linking Reagents; D005782:Gels; D000099166:Polyacrylamides