Amphipathic design dictates self-assembly, cytotoxicity and cell uptake of arginine-rich surfactant-like peptides

Mello, Lucas Rodrigues de; Aguiar, Rodrigo Barbosa de; Yamada, Renata Yoshiko; Moraes, Jane Zveiter de; Hamley, Ian W.; Alves, Wendel A.; Reza, Mehedi; Ruokolainen, Janne; Silva, Emerson Rodrigues da

doi:10.1039/c9tb02219h

Cited by 36 publications

(29 citation statements)

References 61 publications

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“…As exemplified in Figure S3, Ac- R FSFSF R -NH 2 showed three bands at 1630, 1675, and 1695 cm –1 . The band at 1675 cm –1 was assigned to trifluoroacetic acid (TFA) co-existing with the peptides during the synthesis and purification process. , The peaks at 1630 and 1695 cm –1 have been assigned to the characteristic vibration of amide I of β-sheet peptides. , However, the peak at 1695 cm –1 disappeared and a new band at 1643 cm –1 appeared in the case of the isomeric Ac-SF R F R FS-NH 2 , suggesting the largely increased random coil conformation. , Taking the CD, ThT, and FTIR data together, we herein proposed that Ac- R FSFSF R -NH 2 showed the β-sheet character, while Ac-SF R F R FS-NH 2 predominantly adopted the random coil conformation.…”

Section: Results and Discussionmentioning

confidence: 99%

“…More interestingly, the peptide F 4 R 4 with a vesicle-like nanostructure showed the capacity to kill tumor cells. However, the same outcome could not be seen for the analogue R 2 F 4 R 2 . The constitutional isomeric layout has also been exploited to regulate the release of H 2 S into H 9 C 2 cardiomyocytes .…”

Section: Introductionmentioning

confidence: 96%

“…However, the same outcome could not be seen for the analogue R 2 F 4 R 2 . 47 The constitutional isomeric layout has also been exploited to regulate the release of H 2 S into H 9 C 2 cardiomyocytes. 48 Inspired by these findings, we sought to explore how the constitutional isomeric sequence layout could be harnessed to regulate the peptide self-assembly and the final antimicrobial activity.…”

Section: ■ Introductionmentioning

confidence: 99%

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Nano-Antimicrobial Peptides Based on Constitutional Isomerism-Dictated Self-Assembly

Liu

Nie

et al. 2022

Biomacromolecules

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Self-assembly has been identified as an innovative strategy for improving the antimicrobial efficacy and bioavailability of short peptides. However, the detailed molecular information of short peptides linking to the self-assembly structures and antimicrobial activity remains to be more clearly understood. This work reported that the constitutional isomeric sequences of cationic peptides showed a significant impact on their antimicrobial activity. We investigated the self-assembly structures of two constitutional isomeric peptides Ac-RFSFSFR-NH2 and Ac-SFRFRFS-NH2, which contained the same serine, alkaline, and phenylalanine residues but in a different order. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) revealed that the constitutional isomers self-assembled into different morphologies in an aqueous solution. The sequence with alkaline residues located at both termini of the peptide favored the formation of β-sheet conformation and nanofibers, while irregular nanospheres were observed when positioning the alkaline residues at the center of the isomeric peptide. The ζ-potential measurements showed that the Ac-RFSFSFR-NH2 nanofibers had a net potential of +17.4 mV, whereas the apparent potential of Ac-SFRFRFS-NH2 nanospheres dropped steeply to +1.0 mV. These differences of the constitutional isomeric peptides were directly reflected in their antimicrobial activities. In comparison with the peptide Ac-SFRFRFS-NH2, the constitutional isomer Ac-RFSFSFR-NH2 exhibited much higher antimicrobial efficacy against Gram-positive Staphylococcus aureus and Bacillus subtilis and Gram-negative Escherichia coli and Pseudomonas aeruginosa. Moreover, several pairs of constitutional isomeric peptides with a similar sequence layout yielded the same outcome. These collective results not only highlight the importance of the isomeric sequence on the antimicrobial efficacy of short peptides but also increase further potential in optimizing the design of self-assembled nano-antimicrobial peptides (AMPs).

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Section: Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: ■ Introductionmentioning

confidence: 99%

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Nano-Antimicrobial Peptides Based on Constitutional Isomerism-Dictated Self-Assembly

Liu

Nie

et al. 2022

Biomacromolecules

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“…The DGRL 4 DGW sequence has a triblock design, as illustrated in Figure A, where a tetraleucine segment is flanked by more hydrophilic regions at both termini. This feature conveys a bolaamphiphilic design to the strands and favors self-assembly into tapes and fibers, − and nanostructures are able to form hydrogel networks . The presence of fibers with β-sheet conformations as indicated by FTIR and CD led us to test the hypothesis of amyloidogenic features in the gels.…”

Section: Resultsmentioning

confidence: 99%

Nanostructure Formation and Cell Spheroid Morphogenesis of a Peptide Supramolecular Hydrogel

et al. 2022

Self Cite

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Peptide-based hydrogels have attracted much attention due to their extraordinary applications in biomedicine and offer an excellent mimic for the 3D microenvironment of the extracellular matrix. These hydrated matrices comprise fibrous networks held together by a delicate balance of intermolecular forces. Here, we investigate the hydrogelation behavior of a designed decapeptide containing a tetraleucine self-assembling backbone and fibronectin-related tripeptides near both ends of the strand. We have observed that this synthetic peptide can produce hydrogel matrices entrapping >99% wt/vol % water. Ultrastructural analyses combining atomic force microscopy, small-angle neutron scattering, and X-ray diffraction revealed that amyloid-like fibrils form cross-linked networks endowed with remarkable thermal stability, the structure of which is not disrupted up to temperatures >80 °C. We also examined the interaction of peptide hydrogels with either NIH3T3 mouse fibroblasts or HeLa cells and discovered that the matrices sustain cell viability and induce morphogenesis into grape-like cell spheroids. The results presented here show that this decapeptide is a remarkable building block to prepare highly stable scaffolds simultaneously endowed with high water retention capacity and the ability to instruct cell growth into tumor-like spheroids even in noncarcinoma lineages.

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“…[73] AFM is commonly used to measure the height of nanostructures, especially nanoribbons and nanofibers, that are 10 nm or less in thickness. [23,74] Compared to techniques such as SEM and TEM, AFM is more cost-effective and offers comparable resolution. [73] SEM is a type of electron microscopy that generates images using a high-energy beam of electrons directed at a sample's surface.…”

Section: Microscopymentioning

confidence: 99%

Factors Affecting Secondary and Supramolecular Structures of Self‐Assembling Peptide Nanocarriers

Pitz

Nukovic

Elpers

et al. 2021

Macromolecular Bioscience

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Self-assembling peptides are a popular vector for therapeutic cargo delivery due to their versatility, tunability, and biocompatibility. Accurately predicting secondary and supramolecular structures of self-assembling peptides is essential for de novo peptide design. However, computational modeling of such assemblies is not yet able to accurately predict structure formation for many peptide sequences. This review identifies patterns in literature between secondary and supramolecular structures, primary sequences, and applications to provide a guide for informed peptide design. An overview of peptide structures, their applications as nanocarriers, and analytical methods for characterizing secondary and supramolecular structure is examined. A top-down approach is then used to identify trends between peptide sequence and assembly structure from the current literature, including an analysis of the drivers at work, such as local and nonlocal sequence effects and solution conditions.

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Amphipathic design dictates self-assembly, cytotoxicity and cell uptake of arginine-rich surfactant-like peptides

Abstract: Amphiphilicity is the most critical parameter in the self-assembly of surfactant-like peptides, regulating the way by which hydrophobic attraction holds peptides together.

Cited by 36 publications

References 61 publications

Nano-Antimicrobial Peptides Based on Constitutional Isomerism-Dictated Self-Assembly

Nano-Antimicrobial Peptides Based on Constitutional Isomerism-Dictated Self-Assembly

Nanostructure Formation and Cell Spheroid Morphogenesis of a Peptide Supramolecular Hydrogel

Factors Affecting Secondary and Supramolecular Structures of Self‐Assembling Peptide Nanocarriers

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