Letter abstract
Nature Materials 4, 460 - 464 (2005)
doi:10.1038/nmat1392
Subject Categories: Biological materials | Biomedical materials | Mechanical properties
Non-viral gene delivery regulated by stiffness of cell adhesion substrates
Hyun Joon Kong1, Jodi Liu2, Kathryn Riddle2, Takuya Matsumoto1, Kent Leach1 and David J. Mooney1
Non-viral gene vectors are commonly used for gene therapy1, 2, 3 owing to safety concerns with viral vectors4. However, non-viral vectors are plagued by low levels of gene transfection and cellular expression1, 2. Current efforts to improve the efficiency of non-viral gene delivery are focused on manipulations of the delivery vector5, 6, 7, 8, 9, 10, 11, 12, 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 differentiation13, 14, 15, 16, 17, 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) technique18, 19, 20, 21. This study provides a new material-based control point for non-viral gene therapy.
- Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA
- Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA
Correspondence to: David J. Mooney1 e-mail: mooneyd@deas.harvard.edu
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