Cyclic stretching of soft substrates induces spreading and growth.

Yidan Cui,Sungsu Park,Bo Yang,Catherine Qiurong Pan,Kyunghee Lee,Feroz M Hameed,Michael Sheetz

doi:10.1038/ncomms7333

Yidan Cui, Sungsu Park + Show 5 more

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In the body, soft tissues often undergo cycles of stretching and relaxation that may affect cell behaviour without changing matrix rigidity. To determine whether transient forces can substitute for a rigid matrix, we stretched soft pillar arrays. Surprisingly, 1–5% cyclic stretching over a frequency range of 0.01–10 Hz caused spreading and stress fibre formation (optimum 0.1 Hz) that persisted after 4 h of stretching. Similarly, stretching increased cell growth rates on soft pillars comparative to rigid substrates. Of possible factors linked to fibroblast growth, MRTF-A (myocardin-related transcription factor-A) moved to the nucleus in 2 h of cyclic stretching and reversed on cessation; but YAP (Yes-associated protein) moved much later. Knockdown of either MRTF-A or YAP blocked stretch-dependent growth. Thus, we suggest that the repeated pulling from a soft matrix can substitute for a stiff matrix in stimulating spreading, stress fibre formation and growth.

Highlights

In the body, soft tissues often undergo cycles of stretching and relaxation that may affect cell behaviour without changing matrix rigidity
Applying external forces to cells plated on a rigid substrate often leads to cytoskeleton reorganization and strengthening of the focal adhesions due to the cellular tendency to resist the deformation caused by force and to maintain optimum mechanical conditions[6,18,19]
With cyclic stretching of the substrate, the cells spread and grew as if on a rigid substrate. Translocation of both MRTF-A (Myocardin-related transcription factor-A) and YAP (Yes-associated protein) to the nucleus might be involved in this process

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Introduction

Soft tissues often undergo cycles of stretching and relaxation that may affect cell behaviour without changing matrix rigidity. Results and Discussion Cyclic stretch increases cell spreading on soft nanopillars. These cellular responses were consistent with previous reports[11,12,25] showing rigiditydependent cell spreading and stress fibre formation on soft and rigid substrates such as gels and glass.

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