Inhomogeneous substrate strain-driven long-range cellular patterning

Cellular patterning plays a pivotal role in development, tissue function, and homeostasis. Unlike biochemical cues, the effects of various mechanical cues on cellular patterning are still underexplored. One such unexplored mechanical cue is the pre-strain or pre-strain gradient. To address this question, we created a bio-inspired structure by embedding rigid glass objects inside a compliant polyacrylamide (PAA) hydrogel, which, upon swelling, developed a well-defined pre-strain gradient, which was further augmented by cellular traction, resulting in cellular alignment over a remarkably long distance (1–2 mm or 20–40 cell lengths). Such patterning depends on various cellular parameters such as cell length, aspect ratio, traction, and substrate rheological parameters. Furthermore, using high-fidelity finite element simulations, we demonstrated that the surface strain gradient for various embedded rigid structures was predictive of experimental observations. Fundamentally, our findings demonstrated that adherent contractile cells can perceive and respond to pre-strain gradients, even on a linearly elastic substrate.