Combining simulations and experiments for the molecular engineering of multifunctional collagen mimetic peptide-based materials

Hilderbrand, Amber M.; Taylor, Phillip A.; Stanzione, Francesca; LaRue, Mark; Guo, Chen; Jayaraman, Arthi; Kloxin, April M.

doi:10.1039/d0sm01562h

Cited by 10 publications

(15 citation statements)

References 56 publications

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“…One can expect that the smaller curvature of the outer solvophilic layer as compared to the inner solvophilic layer could impose different confinement effects and bending constraints on such semiflexible/stiff molecules. Further, in the ELP-CLP systems, if we use the more sophisticated coarse-grained model of CLP triple helix that can capture the melting of CLP triple helix into CLP single strands, , we can also quantify the extent of melted CLP helices in the inner vs outer solvophilic layers. Lastly, the reconstructed equilibrated structure can also provide insight into the membrane bending rigidity and associated thermal fluctuations of the vesicle structure …”

Section: Resultsmentioning

confidence: 99%

Computational Reverse Engineering Analysis for Scattering Experiments (CREASE) on Vesicles Assembled from Amphiphilic Macromolecular Solutions

Jayaraman

2021

JACS Au

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In this paper we present the development and validation of the "Computational Reverse-Engineering Analysis for Scattering Experiments" (CREASE) method for analyzing scattering results from vesicle structures that are commonly found upon assembly of synthetic, biomimetic, or bioderived amphiphilic copolymers in solution. The two-step CREASE method takes the amphiphilic polymer chemistry and small-angle scattering intensity profile, I exp (q), as input and determines the vesicles' structural features on multiple length scales ranging from assembled vesicle wall's individual layer thicknesses to the monomer-level packing and distribution of polymer conformations. In the first step of CREASE, a genetic algorithm (GA) is used to determine the relevant vesicle dimensions from the input macromolecular solution information and I exp (q) by identifying the structure whose computed scattering profile best matches the input I exp (q). Then in the second step, the GA-determined dimensions are used for molecular reconstruction of the vesicle structure. To validate CREASE for vesicles, we test CREASE on input scattering intensity profiles generated mathematically (termed as in silico I exp (q) vs q) from a variety of vesicle sizes with known dimensions. We also test CREASE on in silico I exp (q) vs q generated from vesicles with dispersity in all relevant dimensions, resembling real experiments. After successful validation of CREASE, we compare the CREASE-determined dimensions against those obtained from the traditional approach of fitting the scattering intensity profile to relevant analytical model in SASVIEW package. We show that CREASE performs better than or as well as the core−multishell analytical model's fitting in SASVIEW in determining vesicle dimensions with dispersity. We also show that CREASE provides structural information beyond those possible from traditional scattering analysis using the core−multishell model, such as the distribution of solvophilic monomers between the vesicle wall's inner and outer layers in the vesicle wall and the chain-level packing within each vesicle layer.

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Section: Resultsmentioning

confidence: 99%

Computational Reverse Engineering Analysis for Scattering Experiments (CREASE) on Vesicles Assembled from Amphiphilic Macromolecular Solutions

Jayaraman

2021

JACS Au

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“…If, during characterization, such changes are detected, consider changing the location of the functional handle (e.g., middle vs end of peptide) or the functional handle identity. Use of molecular dynamic simulations to evaluate the location that will have the least impact on peptide properties may also be of value. − Difficulties visualizing sample . There are a number of reasons sample visualization may be challenging, including poor labeling, low sample concentration, and assembled peptide structure size.…”

Section: Methods 4: Peptide Structure Visualization Within a Hydrogelmentioning

confidence: 99%

Section: Methods 4: Peptide Structure Visualization Within a Hydrogelmentioning

confidence: 99%

Rapid Production of Multifunctional Self-Assembling Peptides for Incorporation and Visualization within Hydrogel Biomaterials

Ford

Kloxin

2021

ACS Biomater. Sci. Eng.

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Peptides are of continued interest for therapeutic applications, from soluble and immobilized ligands that promote desired binding or uptake to self-assembled supramolecular structures that serve as scaffolds in vitro and in vivo. These applications require efficient and scalable synthetic approaches because of the large amounts of material that often are needed for studies of bulk material properties and their translation. In this work, we establish new methods for the synthesis, purification, and visualization of assembling peptides, with a focus on multifunctional collagen mimetic peptides (mfCMPs) relevant for formation and integration within hydrogel-based biomaterials. First, a methodical approach useful for the microwave-assisted synthesis of assembling peptide sequences prone to deletions was established, beginning with the identification of the deleted residues and their locations and followed by targeted use of dual chemistry couplings for those specific residues. Second, purification techniques that integrate the principles of heating and ion displacement with traditional chromatography and dialysis were implemented to improve separation and isolation of the desired multifunctional peptide product, which contained blocks for thermoresponsiveness and ionic interactions. Third, an approach for fluorescent labeling of these mfCMPs, which is orthogonal to their assembly and their covalent incorporation into a bulk hydrogel material, was established, allowing visualization of the resulting hierarchical fibrillar structures in three dimensions within hydrogels using confocal microscopy. The methods presented in this work allow the production of multifunctional peptides in scalable quantities and with minimal deletions, enabling future studies for better understanding of composition−structure−property relationships and for translating these biomaterials into a range of applications. Although mfCMPs are the focus of this work, the methods demonstrated could prove useful for other assembling peptide systems and for the production of peptides more broadly for therapeutic applications.

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“…These studies highlight the utility of nonequilibrium processing on hierarchical self-assembly of synthetic peptides. Rational molecular design of CMPs to promote their assembly into highly ordered nanofibers, hydrogels, vesicles, and nanospheres have also been demonstrated. − …”

Section: Peptide Self-assemblymentioning

confidence: 99%

Peptide Design and Self-assembly into Targeted Nanostructure and Functional Materials

et al. 2021

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Peptides have been extensively utilized to construct nanomaterials that display targeted structure through hierarchical assembly. The self-assembly of both rationally designed peptides derived from naturally occurring domains in proteins as well as intuitively or computationally designed peptides that form β-sheets and helical secondary structures have been widely successful in constructing nanoscale morphologies with well-defined 1-d, 2-d, and 3-d architectures. In this review, we discuss these successes of peptide self-assembly, especially in the context of designing hierarchical materials. In particular, we emphasize the differences in the level of peptide design as an indicator of complexity within the targeted self-assembled materials and highlight future avenues for scientific and technological advances in this field.

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Combining simulations and experiments for the molecular engineering of multifunctional collagen mimetic peptide-based materials

Abstract: Synergistic approach of experiments and simulations to design multifunctional collagen mimetic peptides relevant for the creation of nanostructured soft materials.

Cited by 10 publications

References 56 publications

Computational Reverse Engineering Analysis for Scattering Experiments (CREASE) on Vesicles Assembled from Amphiphilic Macromolecular Solutions

Computational Reverse Engineering Analysis for Scattering Experiments (CREASE) on Vesicles Assembled from Amphiphilic Macromolecular Solutions

Rapid Production of Multifunctional Self-Assembling Peptides for Incorporation and Visualization within Hydrogel Biomaterials

Peptide Design and Self-assembly into Targeted Nanostructure and Functional Materials

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