D-Periodic Collagen-Mimetic Microfibers

Rele, Shyam; Song, Yuhua; Apkarian, Robert P.; Qu, Zhibin; Conticello, Vincent P.; Chaikof, Elliot L.

doi:10.1021/ja0758990

Cited by 208 publications

(193 citation statements)

References 23 publications

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“…Clearly, this fibrillar material is very different from the long, three-dimensional fibrils obtained from 1a and 1b, which also exhibit periodicity (D) reminiscent of collagen. A recent report described a 36-mer peptide that self-assembles into banded collagen-mimetic fibrils driven by multiple electrostatic interactions (34).…”

Section: Discussionmentioning

confidence: 99%

Thrombogenic collagen-mimetic peptides: Self-assembly of triple helix-based fibrils driven by hydrophobic interactions

Cejas

Kinney

Chen

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

149

128

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Collagens are integral structural proteins in animal tissues and play key functional roles in cellular modulation. We sought to discover collagen model peptides (CMPs) that would form triple helices and self-assemble into supramolecular fibrils exhibiting collagen-like biological activity without preorganizing the peptide chains by covalent linkages. This challenging objective was accomplished by placing aromatic groups on the ends of a representative 30-mer CMP, (GPO)10, as with L-phenylalanine and L-pentafluorophenylalanine in 32-mer 1a. Computational studies on homologous 29-mers 1a-d (one less GPO), as pairs of triple helices interacting head-to-tail, yielded stabilization energies in the order 1a > 1b > 1c > 1d, supporting the hypothesis that hydrophobic aromatic groups can drive CMP self-assembly. Peptides 1a-d were studied comparatively relative to structural properties and ability to stimulate human platelets. Although each 32-mer formed stable triple helices (CD) spectroscopy, only 1a and 1b self-assembled into micrometer-scale fibrils. Light microscopy images for 1a depicted long collagen-like fibrils, whereas images for 1d did not. Atomic force microscopy topographical images indicated that 1a and 1b self-organize into microfibrillar species, whereas 1c and 1d do not. Peptides 1a and 1b induced the aggregation of human blood platelets with a potency similar to type I collagen, whereas 1c was much less effective, and 1d was inactive (EC50 potency: 1a/1b Ͼ Ͼ 1c > 1d). Thus, 1a and 1b spontaneously self-assemble into thrombogenic collagen-mimetic materials because of hydrophobic aromatic interactions provided by the special end-groups. These findings have important implications for the design of biofunctional CMPs.biomaterial ͉ platelets ͉ structure-function ͉ supramolecular triplex T he self-association of peptides and proteins into well ordered supramolecular structures is of pivotal importance in normal physiology and pathophysiology, such as in the assembly of collagen fibrils (1), actin filaments (2), and amyloid fibrils (3, 4). Collagens, which constitute a ubiquitous protein family in animals, contribute an essential matrix component to soft tissues and bones (5, 6). A structural hallmark of many collagens is a rope-like triple helix, the architecture of which derives from the interplay of three proline-rich polypeptide strands (e.g., two ␣1 and one ␣2 for type I collagen) (6-8). In the core domain of the triple helix, the amino acid sequence G-X-Y is repeated multiple times, and each glycine amide NH forms a hydrogen bond with the X-position amide carbonyl on an adjacent strand. The X-and Y-positions are often populated by L-proline and 4(R)-hydroxy-L-proline (O; Hyp), respectively, with the latter stabilizing the triple helix by stereoelectronic effects (9) and water-bridged hydrogen bonds (10).To investigate collagen's structure and function, researchers have resorted to using synthetic collagen model peptides (CMPs)

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Section: Discussionmentioning

confidence: 99%

Thrombogenic collagen-mimetic peptides: Self-assembly of triple helix-based fibrils driven by hydrophobic interactions

Cejas

Kinney

Chen

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

149

128

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“…Recently, the introduction of positively charged residues at the N-terminus and negatively charged residues at the C-terminus of a triple-helical peptide was shown to lead to formation of banded periodic fibrils which resemble collagen fibrils. 52 Thus, peptides may be very useful in deciphering the basic principles of collagen self-assembly to supramolecular structures.…”

Section: Self-association Of Peptides As Models For Higher Order Strumentioning

confidence: 99%

Triple‐helical peptides: An approach to collagen conformation, stability, and self‐association

et al. 2008

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Peptides have been an integral part of the collagen triple‐helix structure story, and have continued to serve as useful models for biophysical studies and for establishing biologically important sequence‐structure‐function relationships. High resolution structures of triple‐helical peptides have confirmed the basic Ramachandran triple‐helix model and provided new insights into the hydration, hydrogen bonding, and sequence dependent helical parameters in collagen. The dependence of collagen triple‐helix stability on the residues in its (Gly‐X‐Y)n repeating sequence has been investigated by measuring melting temperatures of host‐guest peptides and an on‐line collagen stability calculator is now available. Although the presence of Gly as every third residue is essential for an undistorted structure, interruptions in the repeating (Gly‐X‐Y)n amino acid sequence pattern are found in the triple‐helical domains of all nonfibrillar collagens, and are likely to play a role in collagen binding and degradation. Peptide models indicate that small interruptions can be incorporated into a rod‐like triple‐helix with a highly localized effect, which perturbs hydrogen bonds and places the standard triple‐helices on both ends out of register. In contrast to natural interruptions, missense mutations which replace one Gly in a triple‐helix domain by a larger residue have pathological consequences, and studies on peptides containing such Gly substitutions clarify their effect on conformation, stability, and folding. Recent studies suggest peptides may also be useful in defining the basic principles of collagen self‐association to the supramolecular structures found in tissues. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 345–353, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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“…55 Though advances have enabled collagen-mimetic peptides to form fibers of 3 to 4 μm in length, these typically involve repeating the same set of peptide sequences in tandem. 56 These alternative strategies rely on identifying specific cell-ECM interactions to engineer the respective known functions. In contrast, our platform utilizes the entire full-length sequence of collagen, which may include uncharacterized epitopes and be beneficial for clinical applications.…”

Section: Discussionmentioning

confidence: 99%

Expanding Functionality of Recombinant Human Collagen Through Engineered Non-Native Cysteines

et al. 2014

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Collagen is the most abundant protein in extracellular matrices and is commonly used as a tissue engineering scaffold. However, collagen and other biopolymers from native sources can exhibit limitations when tuning mechanical and biological properties. Cysteines do not naturally occur within the triple-helical region of any native collagen. We utilized a novel modular synthesis strategy to fabricate variants of recombinant human collagen that contained 2, 4, or 8 non-native cysteines at precisely defined locations within each biopolymer. This bottom-up approach introduced capabilities using sulfhydryl chemistry to form hydrogels and immobilize bioactive factors. Collagen variants retained their triple-helical structure and supported cellular adhesion. Hydrogels were characterized using rheology, and the storage moduli were comparable to fibrillar collagen gels at similar concentrations. Furthermore, the introduced cysteines functioned as anchoring sites, with TGF-β1-conjugated collagens promoting myofibroblast differentiation. This approach demonstrates the feasibility to produce customdesigned collagens with chemical functionality not available from native sources.

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D-Periodic Collagen-Mimetic Microfibers

Cited by 208 publications

References 23 publications

Thrombogenic collagen-mimetic peptides: Self-assembly of triple helix-based fibrils driven by hydrophobic interactions

Thrombogenic collagen-mimetic peptides: Self-assembly of triple helix-based fibrils driven by hydrophobic interactions

Triple‐helical peptides: An approach to collagen conformation, stability, and self‐association

Expanding Functionality of Recombinant Human Collagen Through Engineered Non-Native Cysteines

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