Effect of Peptide and Guest Charge on the Structural, Mechanical and Release Properties of β-Sheet Forming Peptides

Abstract

The effect of peptide charge on the self-assembly, gelation behavior, and model drug release profiles has been explored here for three octa-peptides, VEVKVEVK (VEK2), VKVKVEVK (VEK3), and VEVEVKVE (VEK1), that carry a net charge of 0, +2, and -2 at neutral pH, respectively. Transparent, self-supporting hydrogels were found to form above a critical concentration when the peptide charge modulus was >1 and this was independent of the sign of the charge. TEM, SAXS, and shear rheology revealed that there were no differences in hydrogel structure or mechanical properties when the peptides were at the same concentration and carried the same charge modulus. All peptides were found to form dense fibrillar networks formed by β-sheet rich single fibers where lateral aggregation of the fibers occurred and increased with decreasing charge modulus. Such behavior was found to correlate with an increase in hydrogel mechanical properties, demonstrating that fiber lateral aggregation is inextricably linked with the mechanical properties of these hydrogels. Two hydrophilic model drug molecules, namely napthol yellow (NY) and martius yellow (MY), were subsequently incorporated within the VEK1 and VEK3 hydrogels at pH 7 and although they did not effect the self-assembly of the peptide at a molecular level, they did effect the level of lateral fiber aggregation observed and, therefore, the mechanical properties of the hydrogels. The release of each molecule from the hydrogels was monitored over time and shown to be controlled by Fickian diffusion where the diffusion rate, D, was dependent on the ratio between the overall effective charges carried by the peptide, i.e., the fibrillar network, and the overall charges carried by the guest molecules, but independent from the hydrogel concentration and mechanical properties within the ranges investigated. This work highlights the possibility of controlling the rate of release of small drug molecules by manipulating the charges on the guest molecules as well as the charged state of the self-assembling peptide.

Biomechanical Analysis of Infectious Biofilms

“…Although G ′ (ω) was roughly an order of magnitude larger than G ′′ (ω), indicating elastic-dominated behaviour, the two spectra became comparable on lowering the concentration of Ca 2+ , suggesting a reduction in strong ionic matrix bonds and increased fluidity, consistent with fits to a superposition of wormlike chains [29]. Broadly similar spectra have been observed in a range of polymeric gels, including peptide fibrils [74], block copolymers [77] and intermediate filaments [56]. F pilus producing E. coli biofilms, but not curli producing ones, have also been compared to actin protein gels based on active microrheology experiments [37].…”

Peptide nanofibres as molecular transporters: from self-assembly to in vivo degradation

“…Charged PNFs can repel each other minimizing the aggregation in the system. Roberts et al 24 have shown that for b-sheet forming peptides the net charge of the system, or charge modulus, has to be greater than 1 so that the electrostatic repulsion can prevent fiber aggregation, independent of the sign of the charge. The choice of making the system positively charged rather than negatively charged was based on the consideration that most of the nanoparticles designed for intracellular delivery purposes should be positively charged, to favour the interaction with the moderately negatively charged cell surfaces.…”

In vivo characterisation of a therapeutically relevant self‐assembling 18F‐labelled β‐sheet forming peptide and its hydrogel using positron emission tomography

“…These include their use as scaffolding for 3D cell cultures, tissue engineering and regenerative medicine as well as their use as vehicle for localised drug delivery 1, 2, 3, 4, 5, 6. Peptide hydrogels are made of short synthetic peptides composed of either natural or nonnatural amino acids that are designed to self‐assemble into higher biomimetic structures.…”