Synthetic fibrous hydrogels as a platform to decipher cell-matrix mechanical interactions

Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell func-tions, it remains poorly understood. Key challenges are that the majority of available matrices for such studies, either natural or synthetic, are difficult to control or lack biological relevance. Here, we use a synthetic, yet highly biomimetic hydrogel based on polyisocyanide (PIC) polymers to investigate the effects of the fibrous architec-ture and the nonlinear mechanics on cell-matrix interactions. Live-cell rheology was combined with advanced microscopy-based approaches to understand the mechanisms behind cell-induced matrix stiffening and plastic remodeling. We demonstrate how cell-mediated fiber remodeling and the propagation of fiber displacements are modulated by adjusting the biological and mechanical properties of this material. Moreover, we validate the biological relevance of our results by demonstrating that cellular tractions in PIC gels develop analogously to those in the natural ECM. This study highlights the potential of PIC gels to disentangle complex bidirectional cell-matrix interactions and to improve the design of materials for mechanobiology studies.

Automated summary

Cells sense external forces from the extracellular matrix (ECM) and generate contractile forces to stiffen and remodel the matrix. However, the underlying mechanisms of this bidirectional mechanical exchange are still poorly understood. This study uses a synthetic hydrogel based on polyisocyanide (PIC) polymers to investigate cell-matrix interactions and demonstrates the potential of PIC gels in studying mechanobiology and designing materials.