Fiber Flexibility Reconciles Matrix Recruitment and the Fiber Modulus to Promote Cell Mechanosensing

The mechanical interaction between cells and the extracellular
matrix is pervasive in biological systems. On fibrous substrates,
cells possess the ability to recruit neighboring fibers, thereby augmenting
their own adhesion and facilitating the generation of mechanical cues.
However, the matrices with high moduli impede fiber recruitment, restricting
the cell mechanoresponse. Herein, by harnessing the inherent swelling
properties of gelatin, the flexible gelatin methacryloyl network empowers
cells to recruit fibers spanning a broad spectrum of physiological
moduli during adhesion. The high flexibility concurrently facilitates
the optimization of fiber distribution, deformability, and modulus,
contributing to the promotion of cell mechanosensing. Consequently,
the randomly distributed flexible fibers with high moduli maximize
the cell adhesive forces. This study uncovers the impact of fiber
recruitment on cell mechanosensing and introduces fiber flexibility
as a previously unexplored property, offering an innovative perspective
for the design and development of novel biomaterials.