title: The regulation of integrin-mediated osteoblast focal adhesion and focal adhesion kinase expression by nanoscale topography.
abstract: An important consideration in developing physical biomimetic cell-stimulating cues is that the in vivo extracellular milieu includes nanoscale topographic interfaces. We investigated nanoscale topography regulation of cell functions using human fetal osteoblastic (hFOB) cell culture on poly(l-lactic acid) and polystyrene (50/50 w/w) demixed nanoscale pit textures (14, 29, and 45nm deep pits). Secondary ion mass spectroscopy revealed that these nanotopographic surfaces had similar surface chemistries to that of pure PLLA because of PLLA component surface segregation during spin casting. We observed that 14 and 29nm deep pit surfaces increased hFOB cell attachment, spreading, selective integrin subunit expression (e.g., alphav relative to alpha5, beta1, or beta3), focal adhesive paxillin protein synthesis and paxillin colocalization with cytoskeletal actin stress fibers, and focal adhesion kinase (FAK) and phosphorylated FAK (pY397) expression to a greater degree than did 45nm deep pits or flat PLLA surfaces. Considering the important role of integrin-mediated focal adhesion and intracellular signaling in anchorage-dependent cell function, our results suggest a mechanism by which nanostructured physical signals regulate cell function. Modulation of integrin-mediated focal adhesion and related cell signaling by altering nanoscale substrate topography will have powerful applications in biomaterials science and tissue engineering.
authors.affiliation: Department of Orthopaedics and Rehabilitation, Division of Musculoskeletal Sciences, Center for Biomedical Devices and Functional Tissue Engineering, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
authors.forename: Jung Yul
authors.initials: JY
authors.lastname: Lim
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Dreiss
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zhou
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Hansen
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Siedlecki
authors.forename: Robert W
authors.initials: RW
authors.lastname: Hengstebeck
authors.forename: Juan
authors.initials: J
authors.lastname: Cheng
authors.forename: Nicholas
authors.initials: N
authors.lastname: Winograd
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Donahue
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D002448:Cell Adhesion / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D022001:Focal Adhesions / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure*; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D016023:Integrins; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D051416:Focal Adhesion Protein-Tyrosine Kinases