title: Interplay of cell adhesion matrix stiffness and cell type for non-viral gene delivery.
abstract: Non-viral gene delivery has the potential to treat a wide array of diseases but has been hindered by limited expression in vivo, possibly due to complex cellular microenvironments at delivery sites. Previous studies have reported that extracellular matrix properties, including stiffness, influence non-viral gene transfection efficiencies. This study reports that the effect of matrix stiffness on non-viral gene delivery differs among cell types due to varying sensitivities to matrix rigidity. Plasmid DNA encoding bone morphogenetic protein (BMP)-2 was delivered to fibroblasts, bone marrow stromal cells, and myoblasts cultured on fibronectin-conjugated poly(ethylene glycol) diacrylate hydrogels with varied elastic moduli, and the cellular uptake and subsequent expression of plasmid DNA were examined. While exogenous BMP-2 expression increased with increasing matrix stiffness for all three cell types, the effects of matrix stiffness were most pronounced for fibroblasts. Mechanistic studies conducted in parallel indicate that matrix stiffness influenced the projected area and nuclear aspect ratio for fibroblasts but had minimal effects on the morphology of bone marrow stromal cells and myoblasts. Overall, we believe that the results of this study will be useful for developing advanced non-viral gene delivery strategies for improved therapeutic efficacy.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, IL 61801, USA.
authors.forename: Cathy
authors.initials: C
authors.lastname: Chu
authors.forename: Hyunjoon
authors.initials: H
authors.lastname: Kong
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D021982:Cell-Matrix Junctions / Q000187:drug effects / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D055119:Elastic Modulus / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D018014:Gene Transfer Techniques; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010957:Plasmids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014780:Viruses / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D005353:Fibronectins; D005456:Fluorescent Dyes; D020100:Hydrogels; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols; D004247:DNA