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Ultra-responsive soft matter from strain-stiffening hydrogels.

ABSTRACT: The stiffness of hydrogels is crucial for their application. Nature's hydrogels become stiffer as they are strained. This stiffness is not constant but increases when the gel is strained. This stiffening is used, for instance, by cells that actively strain their environment to modulate their function. When optimized, such strain-stiffening materials become extremely sensitive and very responsive to stress. Strain stiffening, however, is unexplored in synthetic gels since the structural design parameters are unknown. Here we uncover how readily tuneable parameters such as concentration, temperature and polymer length impact the stiffening behaviour. Our work also reveals the marginal point, a well-described but never observed, critical point in the gelation process. Around this point, we observe a transition from a low-viscous liquid to an elastic gel upon applying minute stresses. Our experimental work in combination with network theory yields universal design principles for future strain-stiffening materials.

SUBMITTER: Jaspers M

PROVIDER: S-EPMC4275588 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Ultra-responsive soft matter from strain-stiffening hydrogels.

Jaspers Maarten M Dennison Matthew M Mabesoone Mathijs F J MF MacKintosh Frederick C FC Rowan Alan E AE Kouwer Paul H J PH

Nature communications 20141216

The stiffness of hydrogels is crucial for their application. Nature's hydrogels become stiffer as they are strained. This stiffness is not constant but increases when the gel is strained. This stiffening is used, for instance, by cells that actively strain their environment to modulate their function. When optimized, such strain-stiffening materials become extremely sensitive and very responsive to stress. Strain stiffening, however, is unexplored in synthetic gels since the structural design pa ...[more]

PMID: 25510333

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Project description:The ability to assess changes in smooth muscle contractility and pharmacological responsiveness in normal or pathological-relevant vascular tissue environments is critical to enable vascular drug discovery. However, major challenges remain in both capturing the complexity of in vivo vascular remodeling and evaluating cell contractility in complex, tissue-like environments. Herein, we developed a biomimetic fibrous hydrogel with tunable structure, stiffness, and composition to resemble the native vascular tissue environment. This hydrogel platform was further combined with the combinatory protein array technology as well as advanced approaches to measure cell mechanics and contractility, thus permitting evaluation of smooth muscle functions in a variety of tissue-like microenvironments. Our results demonstrated that biomimetic fibrous structure played a dominant role in smooth muscle function, while the presentation of adhesion proteins co-regulated it to various degrees. Specifically, fibre networks enabled cell infiltration and upregulated expression of actomyosin proteins in contrast to flat hydrogels. Remarkably, fibrous structure and physiologically relevant stiffness of hydrogels cooperatively enhanced smooth muscle contractility and pharmacological responses to vasoactive drugs at both the single cell and intact tissue levels. Together, this study is the first to demonstrate alterations of human vascular smooth muscle contractility and pharmacological responsiveness in biomimetic soft, fibrous environments with a cellular array platform. The integrated platform produced here could enable investigations for pathobiology and pharmacological interventions by developing a broad range of patho-physiologically relevant in vitro tissue models. STATEMENT OF SIGNIFICANCE:Engineering functional smooth muscle in vitro holds the great potential for diseased tissue replacement and drug testing. A central challenge is recapitulating the smooth muscle contractility and pharmacological responses given its significant phenotypic plasticity in response to changes in environment. We present a biomimetic fibrous hydrogel with tunable structure, stiffness, and composition that enables the creation of functional smooth muscle tissues in the native-like vascular tissue microenvironment. Such fibrous hydrogel is further combined with the combinatory protein array technology to construct a cellular array for evaluation of smooth muscle phenotype, contraction, and cell mechanics. The integrated platform produced here could be promising for developing a broad range of normal or diseased in vitro tissue models.

Dataset Information

Ultra-responsive soft matter from strain-stiffening hydrogels.

Publications

Ultra-responsive soft matter from strain-stiffening hydrogels.

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