(386a) "Graduate Student Award Session:" Force-Responsive, Cryptic Hydrogels to Sense and Respond to Cell Traction

Hydrogels are often used as implanted materials for regenerative medicine applications, and increasingly as cell culture substrates to study cells in and on environments with stiffnesses approximating that of real tissues. Hydrogels are relatively soft materials which can weaken under repeated strain and can degrade over time. In contrast, mechano-stiffening biopolymers, particularly proteins that cells interact with in the human body, often strengthen in response to deformation. For example, fibrin, during blood clotting [1], and actin cytoskeletal filaments during cell movement [2], rapidly stiffen under deformations applied by cells [3]. These biopolymers have inspired us to develop a new class of hydrogels that are strain-responsive, yet fully synthetic. As our first attempt at this critical need, we recently published a paper describing the synthesis of responsive organogels with reactive, crosslinkable groups that were initially buried (cryptic) in the network, and only reacted under strain [4]. We demonstrated that strain-induced increases in the Young’s modulus of these organogels; however this first-generation material contained water-insoluble crosslinking groups. We have since adapted this original organogel design to hydrophilic, biocompatible systems via incorporation of the highly hydrophilic zwitterion phosphorylcholine. This new hydrogel system is strain responsive and fully biocompatible. In this presentation I will discuss the design of this material, its ability to crosslink and stiffen under cell-generated traction forces, and its ability to recapitulate the dynamic mechanical environment of the native cell environment.

[1] Janmey, P. A. et al., J. R. Soc. Interface, 2009. 6(30): p. 1-10.

[2] Gardel, M. L. et al. Science, 2004. 304(5675): p. 1301-1305.

[3] Gardel, M. L. et al. Phys. Rev. Lett., 2006. 96(8): p. 088102.

[4] Tran, Y. H. et al. Soft Matter, 2017. 13: p.9007-9014.