- Hadden, William J;
- Young, Jennifer L;
- Holle, Andrew W;
- McFetridge, Meg L;
- Kim, Du Yong;
- Wijesinghe, Philip;
- Taylor-Weiner, Hermes;
- Wen, Jessica H;
- Lee, Andrew R;
- Bieback, Karen;
- Vo, Ba-Ngu;
- Sampson, David D;
- Kennedy, Brendan F;
- Spatz, Joachim P;
- Engler, Adam J;
- Choi, Yu Suk
The spatial presentation of mechanical information is a key parameter for cell behavior. We have developed a method of polymerization control in which the differential diffusion distance of unreacted cross-linker and monomer into a prepolymerized hydrogel sink results in a tunable stiffness gradient at the cell-matrix interface. This simple, low-cost, robust method was used to produce polyacrylamide hydrogels with stiffness gradients of 0.5, 1.7, 2.9, 4.5, 6.8, and 8.2 kPa/mm, spanning the in vivo physiological and pathological mechanical landscape. Importantly, three of these gradients were found to be nondurotactic for human adipose-derived stem cells (hASCs), allowing the presentation of a continuous range of stiffnesses in a single well without the confounding effect of differential cell migration. Using these nondurotactic gradient gels, stiffness-dependent hASC morphology, migration, and differentiation were studied. Finally, the mechanosensitive proteins YAP, Lamin A/C, Lamin B, MRTF-A, and MRTF-B were analyzed on these gradients, providing higher-resolution data on stiffness-dependent expression and localization.