Designed supramolecular filamentous peptides: balance of nanostructure, cytotoxicity and antimicrobial activity

Xu, Dawei; Jiang, Linhai; Singh, Anju; Dustin, Derek; Yang, Miao; Liu, Ling; Lund, Reidar; Sellati, Timothy J.; Dong, He

doi:10.1039/c4cc08808e

Cited by 68 publications

(104 citation statements)

References 48 publications

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“…As demonstrated in our previous work, the site of W is critical to the molecular secondary structure, fiber morphology and antimicrobial activity of SAANs. 21 3W62 exhibited a well-defined β-sheet structure while its isomer W362 formed mixed α-helices and β-sheets. The increased β-sheet content is due to the additional hydrophilic and hydrophobic unit, in this case KW included in the central domain to strengthen the intermolecular interactions among the building blocks.…”

Section: Resultsmentioning

confidence: 99%

“…As reported previously, both peptides self-assembled into short nanofibers. 21 For P-W362, short nanofibers co-exist with substantial amounts of random near spherical aggregates (Figure 3a). The formation of spheres is presumably due to structural denaturation of W362 upon PEG conjugation leading to reorganization of the building block to form non-specific aggregates.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, several cationic synthetic polymers and peptides have been designed and used as the molecular building blocks to form supramolecular assemblies with tunable, nanostructure-dependent antimicrobial activity. 12, 15, 18, 21, 22 …”

Section: Introductionmentioning

confidence: 99%

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Toward hemocompatible self-assembling antimicrobial nanofibers: understanding the synergistic effect of supramolecular structure and PEGylation on hemocompatibility

Ran

Xiang

et al. 2016

RSC Adv.

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A significant challenge associated with systemic delivery of cationic antimicrobial peptides and polymers lies in their limited hemocompatibility toward vast numbers of circulating red blood cells (RBCs). Supramolecular assembly of cationic peptides and polymers can be an effective strategy to develop an array of antimicrobial nanomaterials with tunable material structures, stability and thus optimized bioactivity to overcome some of the existing challenges associated with conventional antimicrobials. In this work, we will demonstrate the supramolecular design of self-assembling antimicrobial nanofibers (SAANs) which have tunable supramolecular nanostructures, stability, internal molecular packing and surface chemistry through self-assembly of de novo designed cationic peptides and peptide-PEG conjuguates. The interaction of the SAANs with human RBCs was evaluated in a stringent biological assay (beyond a traditional hemolysis assay) where both hemolytic and eryptotic activity were examined to establish a fundamental understanding on the correlation between material structure and hemocompatibility. It was found that although the SAANs showed moderate hemolytic activities, their abilities to induce eryptosis vary significantly and are much more sensitive to the internal molecular packing, supramolecular nanostructure and stability of the nanofiber. Improved hemocompatibility requires PEGylation on stable supramolecular nanofibers composed of highly organized β-sheet structure while PEG conjugation on weakly packed nanofibers composed of partially denatured β-sheets did not show improvement. The current study reveals the fundamental mechanism involved in the selective hemocompatibility improvement of the SAANs upon PEG conjugation. The structure-activity relationship developed in this study will provide important guidance for the future design of a broader family of peptide and polymer-based assemblies with optimized antimicrobial activity and hemocompatibility.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Toward hemocompatible self-assembling antimicrobial nanofibers: understanding the synergistic effect of supramolecular structure and PEGylation on hemocompatibility

Ran

Xiang

et al. 2016

RSC Adv.

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“…35 The antimicrobial activity of the soluble peptide nanofiber is inversely related to its β-sheet content. Supramolecular structures with partially folded β-sheets dramatically enhanced the antimicrobial efficacy compared to those consisting of well-defined β-sheets.…”

Section: Introductionmentioning

confidence: 99%

Self-assembly of cationic multidomain peptide hydrogels: supramolecular nanostructure and rheological properties dictate antimicrobial activity

Jiang

Sellati

et al. 2015

Nanoscale

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Hydrogels are an important class of biomaterials that have been widely utilized for a variety of biomedical/medical applications. The biological performance of hydrogels, particularly those used as wound dressing could be greatly advanced if imbued with inherent antimicrobial activity capable of staving off colonization of the wound site by opportunistic bacterial pathogens. Possessing such antimicrobial properties would also protect the hydrogel itself from being adversely affected by microbial attachment to its surface. We have previously demonstrated the broad-spectrum antimicrobial activity of supramolecular assemblies of cationic multi-domain peptides (MDPs) in solution. Here, we extend the 1-D soluble supramolecular assembly to 3-D hydrogels to investigate the effect of the supramolecular nanostructure and its rheological properties on the antimicrobial activity of self-assembled hydrogels. Among designed MDPs, the bactericidal activity of peptide hydrogels was found to follow an opposite trend to that in solution. Improved antimicrobial activity of self-assembled peptide hydrogels is dictated by the combined effect of supramolecular surface chemistry and storage modulus of the bulk materials, rather than the ability of individual peptides/peptide assemblies to penetrate bacterial cell membrane as observed in solution. The structure–property–activity relationship developed through this study will provide important guidelines for designing biocompatible peptide hydrogels with built-in antimicrobial activity for various biomedical applications.

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“…Self-assembly by noncovalent interactions allows shear thinning and recovery and consequent injectability. 15,22,26 MDPs have also been shown to have antimicrobial behavior 27 and can also be modified for a variety of biological activities. 15,28 Specific to angiogenesis, we have developed a MDP covalently bound to a mimic of VEGF-165.…”

Section: Introductionmentioning

confidence: 99%

Controlled Angiogenesis in Peptide Nanofiber Composite Hydrogels

Wickremasinghe

Kumar

Shi

et al. 2015

ACS Biomater. Sci. Eng.

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Multidomain peptide (MDP) nanofibers create scaffolds that can present bioactive cues to promote biological responses. Orthogonal self-assembly of MDPs and growth-factor-loaded liposomes generate supramolecular composite hydrogels. These composites can act as delivery vehicles with time-controlled release. Here we examine the controlled release of placental growth factor-1 (PlGF-1) for its ability to induce angiogenic responses. PlGF-1 was loaded either in MDP matrices or within liposomes bound inside MDP matrices. Scaffolds showed expected rapid infiltration of macrophages. When released through liposomes incorporated in MDP gels (MDP(Lipo)), PlGF-1 modulates HUVEC VEGF receptor activation in vitro and robust vessel formation in vivo. These loaded MDP(Lipo) hydrogels induce a high level of growth-factor-mediated neovascular maturity. MDP(Lipo) hydrogels offer a biocompatible and injectable platform to tailor drug delivery and treat ischemic tissue diseases.

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Designed supramolecular filamentous peptides: balance of nanostructure, cytotoxicity and antimicrobial activity

Cited by 68 publications

References 48 publications

Toward hemocompatible self-assembling antimicrobial nanofibers: understanding the synergistic effect of supramolecular structure and PEGylation on hemocompatibility

Toward hemocompatible self-assembling antimicrobial nanofibers: understanding the synergistic effect of supramolecular structure and PEGylation on hemocompatibility

Self-assembly of cationic multidomain peptide hydrogels: supramolecular nanostructure and rheological properties dictate antimicrobial activity

Controlled Angiogenesis in Peptide Nanofiber Composite Hydrogels

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