Surface tension-driven persistence: How hydrogel interfacial properties regulate fibroblast directional migration

The development of viscoelastic biomaterials with tunable mechanical properties is a key issue in a wide range of applications in mechanobiology. While numerous foregoing works have revealed the impact of bulk matrix stiffness on cellular and multicellular responses, few have examined the effect of interfacial mechanical properties, such as surface tension σ. Owing to the elastocapillarity phenomenon, σ of soft materials can dominate their bulk mechanical properties and thus regulate cellular response. To address this complex issue of mechanotransduction largely overlooked in the literature, this study introduces a new polymer-based hydrogel that provides fine control of σ. This hydrogel is composed of short polyethylene glycol (PEG) elastic units, cross-linked with poly-L-lysine dendrigrafts (DGL). The stiffness and interfacial mechanical properties of this hydrogel are controlled by adjusting the DGL/PEG ratio and mechanically characterized with optical tweezers. This powerful optical technique enables active microrheology and surface micro-indentation to assess, with the same setup, elastic modulus and surface tension. To demonstrate the key impact of σ in mechanotransduction, 2D fibroblast migration experiments are conducted on fibronectin-coated hydrogels. Single-cell trajectories were tracked using epi-fluorescence imaging, and direction and speed autocorrelations were computed and analysed using the "stick-slip" model. This study highlights, for the first time, that cells can adopt directional persistence migration when surface tension increases. Statement of Significance: A hydrogel composed of PEG and poly-L-lysine dendrigraft has been developed to tune the surface tension of soft materials designed to mimic biological tissues. This interfacial mechanical property was successfully characterized using optical tweezers, after which the two-dimension directional persistent motion of fibroblasts was studied according to the surface tension of hydrogel.