Non-viral gene delivery regulated by stiffness of cell adhesion substrates.
Non-viral gene vectors are commonly used for gene therapy owing to safety concerns with viral vectors. However, non-viral vectors are plagued by low levels of gene transfection and cellular expression. Current efforts to improve the efficiency of non-viral gene delivery are focused on manipulations of the delivery vector, whereas the influence of the cellular environment in DNA uptake is often ignored. The mechanical properties (for example, rigidity) of the substrate to which a cell adheres have been found to mediate many aspects of cell function including proliferation, migration and differentiation, and this suggests that the mechanics of the adhesion substrate may regulate a cell's ability to uptake exogeneous signalling molecules. In this report, we present a critical role for the rigidity of the cell adhesion substrate on the level of gene transfer and expression. The mechanism relates to material control over cell proliferation, and was investigated using a fluorescent resonance energy transfer (FRET) technique. This study provides a new material-based control point for non-viral gene therapy.
Kong
Hyun Joon
HJ
Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
Liu
Jodi
J
Riddle
Kathryn
K
Matsumoto
Takuya
T
Leach
Kent
K
Mooney
David J
DJ
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods*; D004548:Elasticity; D015316:Genetic Therapy / Q000379:methods; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics*; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
D020100:Hydrogels; D014677:Pharmaceutical Vehicles; D011094:Polyethyleneimine