Dataset Information

Self-Assembling Multidomain Peptides: Design and Characterization of Neutral Peptide-Based Materials with pH and Ionic Strength Independent Self-Assembly.

ABSTRACT: Self-assembly of peptides is a powerful method of preparing nanostructured materials. These peptides frequently utilize charged groups as a convenient switch for controlling self-assembly in which pH or ionic strength determines the assembly state. Multidomain peptides have been previously designed with charged domains of amino acids, which create molecular frustration between electrostatic repulsion and a combination of supramolecular forces including hydrogen bonding and hydrophobic packing. This frustration is eliminated by the addition of multivalent ions or pH adjustment, resulting in a self-assembled hydrogel. However, these charged functionalities can have profound, unintended effects on the properties of the resulting material. Access to neutral self-assembled nanostructured hydrogels may allow for distinct biological properties that are not available to highly charged analogues. Here, we designed a series of peptides to determine if self-assembly could be mediated by the steric interactions created by neutral hydroxyproline (O) domains, eliminating the need for charged residues and creating a neutral peptide hydrogel. The series of peptides, O n (SL)6O n , was studied to determine the effect of oligo-hydroxyproline on peptide self-assembly and nanostructure. We show that peptide solubility and nanofiber length increase with a higher number of hydroxyproline residues. Within this series, O5(SL)6O5 displayed the optimal properties for self-assembly and hydrogelation. In vitro, this hydrogel supports cell viability of fibroblasts, while in vivo it is infiltrated with cells and easily degraded over time without promoting a strong inflammatory response. This neutral self-assembling peptide hydrogel shows promising properties for biomedical, cell preservation, and tissue regeneration applications.

SUBMITTER: Lopez-Silva TL

PROVIDER: S-EPMC6688848 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Self-Assembling Multidomain Peptides: Design and Characterization of Neutral Peptide-Based Materials with pH and Ionic Strength Independent Self-Assembly.

Lopez-Silva Tania L TL Leach David G DG Li I-Che IC Wang Xinran X Hartgerink Jeffrey D JD

ACS biomaterials science & engineering 20181220 2

Self-assembly of peptides is a powerful method of preparing nanostructured materials. These peptides frequently utilize charged groups as a convenient switch for controlling self-assembly in which pH or ionic strength determines the assembly state. Multidomain peptides have been previously designed with charged domains of amino acids, which create molecular frustration between electrostatic repulsion and a combination of supramolecular forces including hydrogen bonding and hydrophobic packing. T ...[more]

PMID: 31404449

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Project description:Here we report three new nanofibrous, self-assembling multidomain peptide (MDP) sequences and examine the effect of sequence on the morphology and expansion of encapsulated Stem cells from Human Exfoliated Deciduous teeth (SHED). We modified our previously reported set of serine-based MDPs, changing the serine residues in the amphiphilic region to threonine. The three new threonine-based sequences self-assemble into antiparallel ?-sheet nanofibers, confirmed by CD and IR. AFM and negative-stained TEM show that the nanofibers formed by the new sequences are more curved than their serine-containing predecessors. Despite this change in nanofiber morphology, SEM illustrates that all three new sequences still form porous hydrogels. K(TL)2SLRG(TL)3KGRGDS, with a designed cleavage site, is able to be degraded by Matrix Metalloprotease 2. We then examine SHED cell response to these new sequences as well as their serine-based predecessors. We observe faster cell attachment and spreading in hydrogels formed by K2(SL)6K2GRGDS and K(SL)3RG(SL)3KGRGDS. By day 3, the SHEDs in all of the serine-based sequences exhibit a fibroblast-like morphology. Additionally, the SHED cells expand more rapidly in the serine-based gels while the cell number remains relatively constant in the threonine-based peptides. In hydrogels formed by K2(TL)6K2GRGDS and K(TL)2SLRG(TL)3KGRGDS, this low expansion rate is accompanied by changes in morphology where SHEDs exhibit a stellate morphology after 3 days in culture; however, by day 7 they appear more fibroblast-shaped. Throughout the duration of the experiment, the SHED cells encapsulated in the K2(TL)6K2 hydrogels remain rounded. These results suggest that the basic MDP structure easily accommodates modifications in sequence and, for SHED cells, the threonine-containing gels require the integrin-binding RGDS sequence for cell attachment to occur, while the serine-based gels are less selective and support an increase in cell number, regardless of the presence or absence of RGDS.

Project description:Multidomain peptides (MDPs) are a class of self-assembling peptides that are organized in a ?-sheet motif, resulting in a nanofibrous architecture. This structure is stabilized by hydrophobic packing in the fiber core and a hydrogen-bonding network down the fiber long axis. Under easily controllable conditions, regulated by electrostatic interactions between the peptides and the pH and salt composition of the solvent, the nanofiber length can be dramatically extended, resulting in fiber entanglement and hydrogel formation. One of the chief strengths of this supramolecular material is that the design criteria governing its structure and assembly are robust and permit a wide range of modifications without disruption. This allows the MDPs to be tailored to suit a wide range of applications, particularly in biomedical engineering. For example, delivery of small molecules, proteins, and cells is easily achievable. These materials can be trapped within the matrices of the hydrogel or trapped within the hydrophobic core of the nanofiber, depending on the cargo and the design of the MDP. Interactions between the nanofibers and their cargo can be tailored to alter the release profile, and in the most sophisticated cases, different cargos can be released in a cascading time-dependent fashion. The MDP hydrogel and its cargo can be targeted to specific locations, as the thixotropic nature of the hydrogel allows it to be easily aspirated into a syringe and then delivered from a narrow-bore needle. The sequence of amino acids making up the MDP can also be modified to permit cross-linking or enzymatic degradation. Selection of sequences with or without these modifications allows one to control the rate of degradation in vivo from as rapidly as 1 week to well over 6 weeks as the MDP nanofibers are degraded to their amino acid components. MDP sequences can also be modified to add biomimetic sequences derived from growth factors and other signaling proteins. These chemical signals are displayed at a very high density on the fibers' surface, where they contribute to the modification of cellular behavior. We have used this approach to drive blood vessel formation, which is critical for tissue regeneration generally and more specifically for the treatment of diseases related to poor blood flow. MDPs represent an ideal case of bottom-up design where control of chemical structure leads to control of self-assembly and nanostructure and thereby control of material properties that collectively can control biological function.

Dataset Information

Self-Assembling Multidomain Peptides: Design and Characterization of Neutral Peptide-Based Materials with pH and Ionic Strength Independent Self-Assembly.

Publications

Self-Assembling Multidomain Peptides: Design and Characterization of Neutral Peptide-Based Materials with pH and Ionic Strength Independent Self-Assembly.

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