Tunable Mechanics of Peptide Nanofiber Gels

Abstract

The mechanical properties of self-assembled fibrillar networks are influenced by the specific intermolecular interactions that modulate fiber entanglements. We investigate how changing these interactions influences the mechanics of self-assembled nanofiber gels composed of peptide amphiphile (PA) molecules. PAs developed in our laboratory self-assemble into gels of nanofibers after neutralization or salt-mediated screening of the charged residues in their peptide segment. We report here on the gelation, stiffness, and response to deformation of gels formed from a negatively charged PA and HCl or CaCl(2). Scanning electron microscopy of these gels demonstrates a similar morphology, whereas the oscillatory rheological measurements indicate that the calcium-mediated ionic bridges in CaCl(2)-PA gels form stronger intra- and interfiber cross-links than the hydrogen bonds formed by the protonated carboxylic acid residues in HCl-PA gels. As a result, CaCl(2)-PA gels can withstand higher strains than HCl-PA gels. After exposure to a series of strain sweeps with increasing strain amplitude HCl- and CaCl(2)-PA gels both recover 42% of their original stiffness. In contrast, after sustained deformation at 100% strain, HCl-PA gels recover nearly 90% of their original stiffness after 10 min, while the CaCl(2)-PA gels only recover 35%. This result suggests that the hydrogen bonds formed by the protonated acids in the HCl-PA gels allow the gel to relax quickly to its initial state, while the strong calcium cross-links in the CaCl(2)-PA gels lock in the deformed structure and inhibit the gel's ability to recover. We also show that the rheological scaling behaviors of HCl- and CaCl(2)-PA gels are consistent with that of uncross- and cross-linked semiflexible biopolymer networks, respectively. The ability to modify how self-assembled fibrillar networks respond to deformations is important in developing self-assembled gels that can resist and recover from the large deformations that these gels encounter while serving as synthetic cell scaffolds in vivo.

Tunable Pentapeptide Self‐Assembled β‐Sheet Hydrogels

“…Comparing IDIDI (1 wt %) and D2I3 (2 wt %) hydrogels, the G′ value increased by two orders of magnitude from 2 to 200 kPa, respectively. These stiffness values are in the region of many soft tissues and compare well to previously published peptide hydrogel systems, including aromatic peptides4, 17 and peptide–amphiphile hydrogels 27, 28. The ability to tune the G′ value across a large range holds great promise for applications in tissue engineering, given that the behavior of cells has been found to be heavily influenced by the mechanical properties of their surrounding environment 29, 30…”

Low-Molecular-Weight Gels: The State of the Art

“…However, it is clear that similar observations can be found with other examples. Greenfield et al 92 have shown that gels with different properties can be formed from the same peptide amphiphile. As with the 2NapFF above, these can be gelled by the addition of a calcium salt to a solution of the LMWG in water or by the addition of acid.…”

Polymeric Nanofibers in Tissue Engineering

“…59 The mechanical properties of the gels can be controlled by the structure and concentration of PAs; however, the ability to control mechanical properties by modifying the interactions between fibers has also been demonstrated. 60 Pore structure and cellular infiltration Control of pore structure is an important aspect of scaffold fabrication, as it directly affects cell infiltration. Of the three production methods discussed, phase separation allows for the greatest control of pore structure.…”