Early Stiffening and Softening of Collagen: Interplay of Deformation Mechanisms in Biopolymer Networks

Kurniawan, Nicholas A.; Wong, LH Long; Rajagopalan, Raj

doi:10.1021/bm2015812

Cited by 76 publications

(76 citation statements)

References 48 publications

(88 reference statements)

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“…A more elaborative way to interpret kinetics of gelation and to elucidate the impact of crosslinking on the mechanical properties of networks is to convey the phase angle as a function of time. [ 33 ] The storage (G ′ ) and loss (G ′ ′ ) moduli are related by tan( δ ) = G ′ ′ / G ′ , where δ is the phase angle and tan( δ ) is the loss (damping) factor. Gelation takes place if δ falls below 90 ° , or G ′ ′ / G ′ < 1.…”

Section: Bulk Rheological Analyses Of the Cross-linked Supramolecularmentioning

confidence: 99%

Mussel Inspired Dynamic Cross‐Linking of Self‐Healing Peptide Nanofiber Network

Ceylan

Ürel

Erkal

et al. 2012

Adv Funct Materials

127

101

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A general drawback of supramolecular peptide networks is their weak mechanical properties. In order to overcome a similar challenge, mussels have adapted to a pH-dependent iron complexation strategy for adhesion and curing. This strategy also provides successful stiffening and self-healing properties. The present study is inspired by the mussel curing strategy to establish iron cross-link points in self-assembled peptide networks. The impact of peptide-iron complexation on the morphology and secondary structure of the supramolecular nanofi bers is characterized by scanning electron microscopy, circular dichroism and Fourier transform infrared spectroscopy. Mechanical properties of the cross-linked network are probed by small angle oscillatory rheology and nanoindentation by atomic force microscopy. It is shown that iron complexation has no infl uence on self-assembly and β -sheet-driven elongation of the nanofi bers. On the other hand, the organic-inorganic hybrid network of iron cross-linked nanofi bers demonstrates strong mechanical properties comparable to that of covalently cross-linked network. Strikingly, iron cross-linking does not inhibit intrinsic reversibility of supramolecular peptide polymers into disassembled building blocks and the self-healing ability upon high shear load. The strategy described here could be extended to improve mechanical properties of a wide range of supramolecular polymer networks.

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Section: Bulk Rheological Analyses Of the Cross-linked Supramolecularmentioning

confidence: 99%

Mussel Inspired Dynamic Cross‐Linking of Self‐Healing Peptide Nanofiber Network

Ceylan

Ürel

Erkal

et al. 2012

Adv Funct Materials

127

101

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“…These gels undergo stress relaxation in response to an applied strain: the initial stress resisting an applied strain decreases over time due to reorganization processes that relax the stresses in the matrix. In the case of collagen gels typically used for in vitro studies, viscoelasticity and stress relaxation likely arise from unbinding of the weak interactions, such as hydrophobic and electrostatic forces, which hold the fibers in a network (19)(20)(21). Interestingly, recent studies have found that viscoelasticity in synthetic hydrogels used as cell culture substrates can influence cell behaviors such as spreading, proliferation, and differentiation (22-25).…”

mentioning

confidence: 99%

Strain-enhanced stress relaxation impacts nonlinear elasticity in collagen gels

Nam

Butte

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

253

210

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The extracellular matrix (ECM) is a complex assembly of structural proteins that provides physical support and biochemical signaling to cells in tissues. The mechanical properties of the ECM have been found to play a key role in regulating cell behaviors such as differentiation and malignancy. Gels formed from ECM protein biopolymers such as collagen or fibrin are commonly used for 3D cell culture models of tissue. One of the most striking features of these gels is that they exhibit nonlinear elasticity, undergoing strain stiffening. However, these gels are also viscoelastic and exhibit stress relaxation, with the resistance of the gel to a deformation relaxing over time. Recent studies have suggested that cells sense and respond to both nonlinear elasticity and viscoelasticity of ECM, yet little is known about the connection between nonlinear elasticity and viscoelasticity. Here, we report that, as strain is increased, not only do biopolymer gels stiffen but they also exhibit faster stress relaxation, reducing the timescale over which elastic energy is dissipated. This effect is not universal to all biological gels and is mediated through weak cross-links. Mechanistically, computational modeling and atomic force microscopy (AFM) indicate that strain-enhanced stress relaxation of collagen gels arises from force-dependent unbinding of weak bonds between collagen fibers. The broader effect of strain-enhanced stress relaxation is to rapidly diminish strain stiffening over time. These results reveal the interplay between nonlinear elasticity and viscoelasticity in collagen gels, and highlight the complexity of the ECM mechanics that are likely sensed through cellular mechanotransduction.collagen mechanics | viscoelasticity | force-dependent unbinding | biopolymers | stress relaxation T he composition and architecture of ECM is heterogeneous and varies with tissue type and location. One particularly important ECM protein is type Ι collagen, which is the most abundant ECM component and primarily determines the mechanics of connective tissue (1). Type 1 collagen self-assembles into fibers, and these fibers can form networks in vitro. Studies investigating the mechanical properties of collagen networks have revealed that these networks are nonlinearly elastic and exhibit strain stiffening, or an increase in the elasticity as the strain on the network is enhanced (1-3). This nonlinear elasticity is also a characteristic feature of fibrin gels, which serve as the major component of blood clots, as well as in reconstituted networks of intermediate filaments and cytoskeletal actin networks (2, 4-7). These networks are all composed of semiflexible polymers or fibers, which are relatively rigid, so that the tangent to the contour of the polymer is correlated over long lengths, yet undergo substantial bending fluctuations due to thermal energy. Semiflexible polymers or fibers form networks at low volume fractions (8). Strain stiffening in these networks is thought to arise from either the entropic elasticity of single polymers...

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“…More specifically, at small strains (less than 10%) the gels soften slightly with an increase in strain, followed by a rapid increase in the elastic modulus with strain. Both strain-softening [31] and strain-stiffening [31,34] responses have been previously reported in collagen networks, although the microstructural origins are still under intense investigations. Importantly, these observations imply that collagen gels are nonlinear elastic materials [35], implying that its mechanical property can be altered by the amount of deformations in the gels.…”

Section: Mechanical Characterization Of Collagen Matricesmentioning

confidence: 99%

Mechanistic adaptability of cancer cells strongly affects anti-migratory drug efficacy

Sun

Lim

Kurniawan

2014

J. R. Soc. Interface.

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Cancer metastasis involves the dissemination of cancer cells from the primary tumour site and is responsible for the majority of solid tumour-related mortality. Screening of anti-metastasis drugs often includes functional assays that examine cancer cell invasion inside a three-dimensional hydrogel that mimics the extracellular matrix (ECM). Here, we built a mechanically tuneable collagen hydrogel model to recapitulate cancer spreading into heterogeneous tumour stroma and monitored the three-dimensional invasion of highly malignant breast cancer cells, MDA-MB-231. Migration assays were carried out in the presence and the absence of drugs affecting four typical molecular mechanisms involved in cell migration, as well as under five ECMs with different biophysical properties. Strikingly, the effects of the drugs were observed to vary strongly with matrix mechanics and microarchitecture, despite the little dependence of the inherent cancer cell migration on the ECM condition. Specifically, cytoskeletal contractility-targeting drugs reduced migration speed in sparse gels, whereas migration in dense gels was retarded effectively by inhibiting proteolysis. The results corroborate the ability of cancer cells to switch their multiple invasion mechanisms depending on ECM condition, thus suggesting the importance of factoring in the biophysical properties of the ECM in anti-metastasis drug screenings.

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Early Stiffening and Softening of Collagen: Interplay of Deformation Mechanisms in Biopolymer Networks

Cited by 76 publications

References 48 publications

Mussel Inspired Dynamic Cross‐Linking of Self‐Healing Peptide Nanofiber Network

Mussel Inspired Dynamic Cross‐Linking of Self‐Healing Peptide Nanofiber Network

Strain-enhanced stress relaxation impacts nonlinear elasticity in collagen gels

Mechanistic adaptability of cancer cells strongly affects anti-migratory drug efficacy

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