How cells sense extracellular matrix stiffness: a material's perspective

•Mechanical properties of the extracellular matrix (ECM) regulate cell fate decisions.•Protein gels mimic in vivo ECM.•Synthetic gels allow for the isolation of mechanics from other structural parameters.•New synthetic ECMs recreate the fibrous structural hierarchy of in vivo ECMs.

The mechanical properties of the extracellular matrix (ECM) in which cells reside have emerged as an important regulator of cell fate. While materials based on natural ECM have been used to implicate the role of substrate stiffness for cell fate decisions, it is difficult in these matrices to isolate mechanics from other structural parameters. In contrast, fully synthetic hydrogels offer independent control over physical and adhesive properties. New synthetic materials that also recreate the fibrous structural hierarchy of natural matrices are now being designed to study substrate mechanics in more complex ECMs. This perspective examines the ways in which new materials are being used to advance our understanding of how ECM stiffness impacts cell function.

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