posted on 2020-08-10, 10:26authored byAmin Liu, Kai Wu, Suping Chen, Chengheng Wu, Dong Gao, Lu Chen, Dan Wei, Hongrong Luo, Jing Sun, Hongsong Fan
As a key mechanical
signal of natural extracellular matrix (ECM),
stress relaxation plays an essential role in cell fate decision. However,
the biomimetic matrix with fast stress relaxation and its cellular
response mechanism have received little attention. Meanwhile, the
nanofibrillar architecture which is conductive to mechanical transduction
has invariably been ignored in the previous viscoelastic matrix design.
Herein, by introducing a dynamic covalent imine bond into a physically
cross-linked collagen hydrogel, we prepared bionic fast-relaxing nanofibrillar
hydrogels with relaxation time less than 10 s. Through a single control
of imine bond content, we realized fine-tuning of the relaxation rate
while maintaining a constant initial modulus and fiber density. Using
MC3T3-E1 cells as a model, we then proved that the nanofibrillar matrix
with fast relaxation mechanics can effectively promote cell spreading
and differentiation. In particular, TRPV4 as a molecular sensor of
matrix viscoelasticity was demonstrated to regulate cell fate on the
nanofibrillar hydrogels by mediating calcium influx. It is expected
that the material design principle combining both nanofibrillar structure
and tunable fast-relaxation can provide a more broadly adaptable materials
platform for simulating natural ECM mechanical cues, and the investigation
of the TRPV4 ion channel mediated cellular response will facilitate
discovery of more fundamental mechanisms in tissue growth and development.