Controlling network topology and mechanical properties of co‐assembling peptide hydrogels

Abstract

Oligopeptides are well-known to self-assemble into a wide array of nanostructures including β-sheet-rich fibers that when present above a critical concentration become entangled and form self-supporting hydrogels. The length, quantity, and interactions between fibers influence the mechanical properties of the hydrogel formed and this is typically achieved by varying the peptide concentration, pH, ionic strength, or the addition of a second species or chemical cross-linking agent. Here, we outline an alternative, facile route to control the mechanical properties of the self-assembling octa-peptide, FEFEFKFK (FEKII); simply doping with controlled quantities of its double length peptide, FEFEFKFK-GG-FKFKFEFE (FEKII18). The structure and properties of a series of samples were studied here (0–100 M% of FEKII18) using Fourier transform infrared, small angle X-ray scattering, transmission electron microscopy, and oscillatory rheology. All samples were found to contain elongated, flexible fibers and all mixed samples contained Y-shaped branch points and parallel fibers which is attributed to the longer peptide self-assembling within two fibers, thus creating a cross-link in the network structure. Such behavior was reflected in an increase in the elasticity of the mixed samples with increasing quantity of double peptide. Interestingly the elastic modulus increased up to 30 times the pure FEKII value simply by adding 28 M% of FEKII18. These observations provide an easy, off-the-shelf method for an end-user to control the cross-linked network structure of the peptide hydrogel, and consequently strength of the hydrogel simply by physically mixing pre-determined quantities of two similar peptide molecules.

Structure–mechanical property correlations of hydrogel forming β-sheet peptides

“…111 Peptide cross linking was assessed by SAXS, TEM and FTIR and interestingly, the storage modulus G 0 of the mixed peptide system increased up to 30 times relative to a hydrogel of the octapeptide (Table 2), thus confirming the utility of the method to generate stiffer hydrogels. The longer peptide was conceived with the idea of favouring incorporation within two separate b-sheet fibrils of the octapeptide, thus forming a controllable number of cross-links/branch points in the fibrillar network.…”

A novel calix[4]arene-based dimeric-cholesteryl derivative: synthesis, gelation and unusual properties

“…S3. As can be seen from the figure, the storage modulus G′ of the three gels are always greater than the loss modulus G′′ with the angular frequency gradually increased from 0.1 rad ⋅ s -1 to 628.0 rad ⋅ s -1 , indicating that there has been no phase transition during the test and the system is a true gel 52. Additionally, the values of G′ and G′′ do not change significantly and after removing the shear force.…”

Tuning of hydrogel stiffness using a two‐component peptide system for mammalian cell culture

“…22,[29][30][31][32] Another example that improved peptide gel strength and systematically controlled the mechanical properties of peptide hydrogels, was based on mixing various quantities of self-assembling ioniccomplementary peptide FEFEFKFK (FEKII8) and its double length counterpart FEFEFKFK-GG-FKFKFEFE (FEKII18). 20 While the hydrogels obtained in water solutions show a G 0 for FEKII8 of 80 AE 5 Pa, when FEKII18 is added to FEKII8 network an increase of G 0 of 30 times is achieved. However, the reached stiffness, while appropriate for cells growing on soft tissues would not be appropriate for other applications in tissue engineering, such as cartilage or bone scaffolds.…”

“…An alternative strategy to tune properties of the hydrogel is to use multicomponent systems, where the mixed self‐assembling peptides can differ with point amino acid substitution, or can be unrelated . Another example that improved peptide gel strength and systematically controlled the mechanical properties of peptide hydrogels, was based on mixing various quantities of self‐assembling ionic‐complementary peptide FEFEFKFK (FEKII8) and its double length counterpart FEFEFKFK‐GG‐FKFKFEFE (FEKII18) . While the hydrogels obtained in water solutions show a G′ for FEKII8 of 80 ± 5 Pa, when FEKII18 is added to FEKII8 network an increase of G′ of 30 times is achieved.…”

“…Several studies have shown peptide hydrogel systems with tuneable stiffness, where tuning is mainly achieved by varying peptide concentrations in the hydrogels. [19][20][21] Some attempts to change hydrogel stiffness by varying amino acid composition in peptide amphiphilic systems has been explored, highlighting the key role of hydrophobic interactions in gel stiffness. 22,23 A similar effect on gel strength can be obtained by varying salt concentration, when charged amino acids are present in the peptide sequence.…”