The modulus of the extracellular matrix is a dynamic property that can both be dictated by resident cells and control cell fate. Until recently, many in vitro substrates for cell culture exhibited static material properties, which required replating cells to study the effects of different moduli on cell phenotype. In addition, many stimuli-responsive substrates rely on additional chemical reactions to modify the polymeric network and hence the modulus. In the work presented here, a strategy is introduced to reversibly control matrix properties without altering network connectivity. Specifically, azobenzene photoisomers are incorporated into the crosslinkers of a 3D poly(ethylene glycol)-based hydrogel to modulate the matrix elasticity in a reversible manner with a wavelength-specific light stimulus. We find that upon irradiation with cytocompatible doses of UV light (365 nm, 10 mW/cm2, 2 min), the photoisomerization disrupts hydrogen bonds from the surrounding network, leading to a decrease in matrix elasticity (12-150 Pa) that is fully recovered upon thermal relaxation or the reverse isomerization of the azobenzene with visible light (400-500 nm, 10 mW/cm2, 2 min). The resulting change in modulus depends on the number of azobenzene photoisomers incorporated into the polymeric network, up to a maximum concentration above which no matrix switching is observed. The incorporated photoswitch was carefully chosen to maximize the lifetime of the cis state, leading to half-lives of 162 hours at 25°C and 9 hours at 37°C. Cytocompatibility was demonstrated with porcine aortic valvular interstitial cells. The developed networks should enable user-defined, noninvasive control of matrix mechanics in the presence of cells. Furthermore, the changes in modulus are reversible and sensitive to the provided light stimulus, allowing for precise changes in the polymeric hydrogel and thus enabling detailed questions in mechanobiology.

Light-responsive strategy for reversible control of elastic modulus in PEG-based hydrogels

249th National Meeting (2015)

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