Maarten Jaspers

Responsive biomimetic networks from polyisocyanopeptide hydrogels

Mechanical responsiveness is essential to all biological systems down to the level of tissues and cells. The intra- and extracellular mechanics of such systems are governed by a series of proteins, such as microtubules, actin, intermediate filaments and collagen. As a general design motif, these proteins self-assemble into helical structures and superstructures that differ in diameter and persistence length to cover the full mechanical spectrum. Gels of cytoskeletal proteins display particular mechanical responses (stress stiffening) that until now have been absent in synthetic polymeric and low-molar-mass gels. Here we present synthetic gels that mimic in nearly all aspects gels prepared from intermediate filaments. They are prepared from polyisocyanopeptides grafted with oligo(ethylene glycol) side chains. These responsive polymers possess a stiff and helical architecture, and show a tunable thermal transition where the chains bundle together to generate transparent gels at extremely low concentrations. Using characterization techniques operating at different length scales (for example, macroscopic rheology, atomic force microscopy and molecular force spectroscopy) combined with an appropriate theoretical network model, we establish the hierarchical relationship between the bulk mechanical properties and the single-molecule parameters. Our results show that to develop artificial cytoskeletal or extracellular matrix mimics, the essential design parameters are not only the molecular stiffness, but also the extent of bundling. In contrast to the peptidic materials, our polyisocyanide polymers are readily modified, giving a starting point for functional biomimetic hydrogels with potentially a wide variety of applications, in particular in the biomedical field.

Ultra-responsive soft matter from strain-stiffening hydrogels

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.

Bundle Formation in Biomimetic Hydrogels

Bundling of single polymer chains is a crucial process in the formation of biopolymer network gels that make up the extracellular matrix and the cytoskeleton. This bundled architecture leads to gels with distinctive properties, including a large-pore-size gel formation at very low concentrations and mechanical responsiveness through nonlinear mechanics, properties that are rarely observed in synthetic hydrogels. Using small-angle X-ray scattering (SAXS), we study the bundle formation and hydrogelation process of polyisocyanide gels, a synthetic material that uniquely mimics the structure and mechanics of biogels. We show how the structure of the material changes at the (thermally induced) gelation point and how factors such as concentration and polymer length determine the architecture, and with that, the mechanical properties. The correlation of the gel mechanics and the structural parameters obtained from SAXS experiments is essential in the design of future (synthetic) mimics of biopolymer networks.

Fibrin-fiber architecture influences cell spreading and differentiation

ABSTRACT The mechanical and structural properties of the extracellular matrix (ECM) play an important role in regulating cell fate. The natural ECM has a complex fibrillar structure and shows nonlinear mechanical properties, which are both difficult to mimic synthetically. Therefore, systematically testing the influence of ECM properties on cellular behavior is very challenging. In this work we show two different approaches to tune the fibrillar structure and mechanical properties of fibrin hydrogels. Addition of extra thrombin before gelation increases the protein density within the fibrin fibers without significantly altering the mechanical properties of the resulting hydrogel. On the other hand, by forming a composite hydrogel with a synthetic biomimetic polyisocyanide network the protein density within the fibrin fibers decreases, and the mechanics of the composite material can be tuned by the PIC/fibrin mass ratio. The effect of the changes in gel structure and mechanics on cellular behavior are investigated, by studying human mesenchymal stem cell (hMSC) spreading and differentiation on these gels. We find that the trends observed in cell spreading and differentiation cannot be explained by the bulk mechanics of the gels, but correlate to the density of the fibrin fibers the gels are composed of. These findings strongly suggest that the microscopic properties of individual fibers in fibrous networks play an essential role in determining cell behavior.

Nonlinear mechanics of hybrid polymer networks that mimic the complex mechanical environment of cells

The mechanical properties of cells and the extracellular environment they reside in are governed by a complex interplay of biopolymers. These biopolymers, which possess a wide range of stiffnesses, self-assemble into fibrous composite networks such as the cytoskeleton and extracellular matrix. They interact with each other both physically and chemically to create a highly responsive and adaptive mechanical environment that stiffens when stressed or strained. Here we show that hybrid networks of a synthetic mimic of biological networks and either stiff, flexible and semi-flexible components, even very low concentrations of these added components, strongly affect the network stiffness and/or its strain-responsive character. The stiffness (persistence length) of the second network, its concentration and the interaction between the components are all parameters that can be used to tune the mechanics of the hybrids. The equivalence of these hybrids with biological composites is striking.

Solid-state NMR characterization of tri-ethyleneglycol grafted polyisocyanopeptides

In aqueous media, ethylene glycol substituted polyisocyanopeptides (PICPs) change their state (undergo a sol‐to‐gel transition) as a response to temperature. This makes them promising materials for various biomedical applications, for instance, for controlled drug release and non‐damaging wound dressing. To utilize PICP in biomedical applications, understanding of the origin of the gelation process is needed, but this is experimentally difficult because of the notoriously low gelator concentration in combination with the slow polymer dynamics in the sample. This paper describes a detailed characterization of the dried state of PICPs by solid‐state NMR measurements. Both the 13C and the 1H NMR resonances were assigned using a combination of 1D cross‐polarization magic angle spinning, 2D 13C–1H heteronuclear correlation spectra and 1H–1H single quantum–double quantum experiments. In addition, the chemical groups involved in dipolar interaction with each other were used to discuss the dynamics and spatial conformation of the polymer. In contrast to other PICP polymers, two resonances for the backbone carbon are observed, which are present in equal amounts. The possible origin of these resonances is discussed in the last section of this work. The data obtained during the current studies will be further used in elucidating mechanisms of the bundling and gelation. A comprehensive picture will make it possible to tailor polymer properties to meet specific needs in different applications. Copyright

Critical behaviour in the nonlinear elastic response of hydrogels

In this paper we study the elastic response of synthetic hydrogels to an applied shear stress. The hydrogels studied here have previously been shown to mimic the behaviour of biopolymer networks when they are sufficiently far above the gel point. We show that near the gel point they exhibit an elastic response that is consistent with the predicted critical behaviour of networks near or below the isostatic point of marginal stability. This point separates rigid and floppy states, distinguished by the presence or absence of finite linear elastic moduli. Recent theoretical work has also focused on the response of such networks to finite or large deformations, both near and below the isostatic point. Despite this interest, experimental evidence for the existence of criticality in such networks has been lacking. Using computer simulations, we identify critical signatures in the mechanical response of sub-isostatic networks as a function of applied shear stress. We also present experimental evidence consistent with these predictions. Furthermore, our results show the existence of two distinct critical regimes, one of which arises from the nonlinear stretch response of semi-flexible polymers.