Enhanced Neuron Growth and Electrical Activity by a Supramolecular Netrin-1 Mimetic Nanofiber

Smith, Cara S.; Álvarez, Zaida; Qiu, Ruomeng; Sasselli, Ivan R.; Clemons, Tristan; Ortega, J. Alberto; Vilela-Picos, Marcos; Wellman, Haley; Kiskinis, Evangelos; Stupp, Samuel I.

doi:10.1021/acsnano.3c04572

Cited by 9 publications

(8 citation statements)

References 87 publications

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“…PAs were synthesized using previously reported protocols for Fmoc solid-phase peptide synthesis synthesized using a CEM Liberty Blue microwave-assisted peptide synthesizer. 30 PAs labeled with cyanine dyes were synthesized also following a previously established method. 47 All PA batches were confirmed to be at least 95% pure by liquid chromatography-electrospray ionization mass spectrometry (ESI-MS, Agilent 6510 Q-TOF) (SI Section I).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…These systems also form highly functional three-dimensional networks upon addition of physiological electrolytes . These materials are of great interest due to their potential use as ECM-like scaffolds for regenerative medicine and delivery vehicles for proteins. , PAs can be functionalized with bioactive signals to further mimic natural ECM tissue by incorporating various epitopes from ECM proteins for neural regeneration, ,, bone growth, angiogenesis, and cartilage regeneration, among others. In our previous work, when charged groups and ionic strength of aqueous solutions were altered, we observed self-sorting behavior in PA nanofibers with the same peptide sequences .…”

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confidence: 99%

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Self-Sorting vs Coassembly in Peptide Amphiphile Supramolecular Nanostructures

Sangji,

Lee,

Sai

et al. 2024

ACS Nano

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The functionality of supramolecular nanostructures can be expanded if systems containing multiple components are designed to either self-sort or mix into coassemblies. This is critical to gain the ability to craft selfassembling materials that integrate functions, and our understanding of this process is in its early stages. In this work, we have utilized three different peptide amphiphiles with the capacity to form β-sheets within supramolecular nanostructures and found binary systems that self-sort and others that form coassemblies. This was measured using atomic force microscopy to reveal the nanoscale morphology of assemblies and confocal laser scanning microscopy to determine the distribution of fluorescently labeled monomers. We discovered that PA assemblies with opposite supramolecular chirality self-sorted into chemically distinct nanostructures. In contrast, the PA molecules that formed a mixture of right-handed, left-handed, and flat nanostructures on their own were able to coassemble with the other PA molecules. We attribute this phenomenon to the energy barrier associated with changing the handedness of a β-sheet twist in a coassembly of two different PA molecules. This observation could be useful for designing biomolecular nanostructures with dual bioactivity or interpenetrating networks of PA supramolecular assemblies.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Self-Sorting vs Coassembly in Peptide Amphiphile Supramolecular Nanostructures

Sangji,

Lee,

Sai

et al. 2024

ACS Nano

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“… ,, While it is often a valid simplified approach, it is only an accurate representation of the experimental system if, for instance, monomers are mixed in a solvent where they are not preassembled/aggregated, such as hexafluoroisopropanol (HFIP) . Otherwise, simulating the coassembly of preassembled components provides a more accurate representation. , This has been employed to incorporate functionalized monomers into filaments, built or assembled in a previous step. ,, The results provided insights into the percentage of incorporation and the presentation of the bioactive sequences, demonstrating excellent correlation with biological in vitro and in vivo experiments.…”

Section: System Size Concentration Time Scale and Initial Structuresmentioning

confidence: 99%

“…The most captivating result of MD is to examine the morphology of supramolecular assemblies, which can be visualized with VMD, Chimera, Pymol, or Morphoscanner, providing qualitative information. In self-assembling simulations, they serve as proof of self-assembly and their morphology can be compared with experimental techniques such as TEM, SEM, AFM, and SAXS. ,,, Their morphological structures can be quantitatively studied through geometry maps (Figure ), obtaining parameters that can be directly validated with experiments . The tools are derived from protein data, making the obtention of specific parameters for multimolecular systems highly challenging.…”

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confidence: 99%

Tips and Tricks in the Modeling of Supramolecular Peptide Assemblies

Piskorz,

Perez-Chirinos,

Qiao

et al. 2024

ACS Omega

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Supramolecular peptide assemblies (SPAs) hold promise as materials for nanotechnology and biomedicine. Although their investigation often entails adapting experimental techniques from their protein counterparts, SPAs are fundamentally distinct from proteins, posing unique challenges for their study. Computational methods have emerged as indispensable tools for gaining deeper insights into SPA structures at the molecular level, surpassing the limitations of experimental techniques, and as screening tools to reduce the experimental search space. However, computational studies have grappled with issues stemming from the absence of standardized procedures and relevant crystal structures. Fundamental disparities between SPAs and protein simulations, such as the absence of experimentally validated initial structures and the importance of the simulation size, number of molecules, and concentration, have compounded these challenges. Understanding the roles of various parameters and the capabilities of different models and simulation setups remains an ongoing endeavor. In this review, we aim to provide readers with guidance on the parameters to consider when conducting SPA simulations, elucidating their potential impact on outcomes and validity.

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A Roadmap of Peptide‐Based Materials in Neural Regeneration

Tsai,

Song,

Shi

et al. 2024

Adv Healthcare Materials

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Injuries to the nervous system lead to irreversible damage and limited functional recovery. The peripheral nervous system (PNS) can self‐regenerate to some extent for short nerve gaps. In contrast, the central nervous system (CNS) has an intrinsic limitation to self‐repair owing to its convoluted neural microenvironment and inhibitory response. The primary phase of CNS injury, happening within 48 h, results from external impacts like mechanical stress. Afterward, the secondary phase of the injury occurs, originating from neuronal excitotoxicity, mitochondrial dysfunction, and neuroinflammation. No golden standard to treat injured neurons exists, and conventional medicine serves only as a protective approach to alleviating the symptoms of chronic injury. Synthetic peptides provide a promising approach for neural repair, either as soluble drugs or by using their intrinsic self‐assembly propensity to serve as an extracellular matrix (ECM) mimic for cell adhesion and to incorporate bioactive epitopes. In this review, an overview of nerve injury models, common in vitro models, and peptide‐based therapeutics such as ECM mimics is provided. Due to the complexity of treating neuronal injuries, a multidisciplinary collaboration between biologists, physicians, and material scientists is paramount. Together, scientists with complementary expertise will be required to formulate future therapeutic approaches for clinical use.

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Enhanced Neuron Growth and Electrical Activity by a Supramolecular Netrin-1 Mimetic Nanofiber

Cited by 9 publications

References 87 publications

Self-Sorting vs Coassembly in Peptide Amphiphile Supramolecular Nanostructures

Self-Sorting vs Coassembly in Peptide Amphiphile Supramolecular Nanostructures

Tips and Tricks in the Modeling of Supramolecular Peptide Assemblies

A Roadmap of Peptide‐Based Materials in Neural Regeneration

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