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Samuel I. Stupp - One of the best experts on this subject based on the ideXlab platform.

  • chiral recognition of lipid bilayer membranes by supramolecular assemblies of Peptide Amphiphiles
    ACS Biomaterials Science & Engineering, 2019
    Co-Authors: Kohei Sato, Zaida Alvarez, Wei Ji, Liam C Palmer, Samuel I. Stupp
    Abstract:

    On the basis of the exclusive existence of homochirality in biomolecules and the well-known phenomenon of chiral recognition, it is obvious that chirality is a crucial factor in biological events. We report here that supramolecular assemblies of Peptide Amphiphiles interact with lipid bilayer membranes in a stereospecific manner. When negatively charged chiral phospholipid bilayer vesicles were subjected to the assemblies, we found that Peptide Amphiphiles with l-amino acids show stronger affinity for the liposomes compared to the ones with d-amino acids. To examine their biological functions, we tested the cytotoxicity of nanofibers against mammalian primary cells using human bone marrow mesenchymal stem cells and murine astroglial cells. We demonstrated that cell viability increased when d-amino acids were incorporated in the structure of Peptide Amphiphiles, which is consistent with our finding of their weaker interactions with lipid bilayer membranes.

  • calcium induced morphological transitions in Peptide Amphiphiles detected by 19f magnetic resonance imaging
    ACS Applied Materials & Interfaces, 2017
    Co-Authors: Adam T Preslar, Samuel I. Stupp, Kohei Sato, Laura M Lilley, Shanrong Zhang, Zer Keen Chia, Thomas J Meade
    Abstract:

    Misregulation of extracellular Ca2+ can indicate bone-related pathologies. New, noninvasive tools are required to image Ca2+ fluxes and fluorine magnetic resonance imaging (19F-MRI) is uniquely suited to this challenge. Here, we present three, highly fluorinated Peptide Amphiphiles that self-assemble into nanoribbons in buffered saline and demonstrate these nanostructures can be programmed to change 19F-NMR signal intensity as a function of Ca2+ concentration. We determined these nanostructures show significant reduction in 19F-NMR signal as nanoribbon width increases in response to Ca2+, corresponding to 19F-MR image intensity reduction. Thus, these Peptide Amphiphiles can be used to quantitatively image biologically relevant Ca2+ concentrations.

  • supramolecular assembly of Peptide Amphiphiles
    Accounts of Chemical Research, 2017
    Co-Authors: Mark P Hendricks, Liam C Palmer, Kohei Sato, Samuel I. Stupp
    Abstract:

    ConspectusPeptide Amphiphiles (PAs) are small molecules that contain hydrophobic components covalently conjugated to Peptides. In this Account, we describe recent advances involving PAs that consist of a short Peptide sequence linked to an aliphatic tail. The Peptide sequence can be designed to form β-sheets among the amino acids near the alkyl tail, while the residues farthest from the tail are charged to promote solubility and in some cases contain a bioactive sequence. In water, β-sheet formation and hydrophobic collapse of the aliphatic tails induce assembly of the molecules into supramolecular one-dimensional nanostructures, commonly high-aspect-ratio cylindrical or ribbonlike nanofibers. These nanostructures hold significant promise for biomedical functions due to their ability to display a high density of biological signals on their surface for targeting or to activate pathways, as well as for biocompatibility and biodegradable nature.Recent studies have shown that supramolecular systems, such as P...

  • co assembly of Peptide Amphiphiles and lipids into supramolecular nanostructures driven by anion π interactions
    Journal of the American Chemical Society, 2017
    Co-Authors: Zhilin Yu, Liam C Palmer, Aykut Erbas, Faifan Tantakitti, Joshua A Jackman, Monica Olvera De La Cruz, Samuel I. Stupp
    Abstract:

    Co-assembly of binary systems driven by specific non-covalent interactions can greatly expand the structural and functional space of supramolecular nanostructures. We report here on the self-assembly of Peptide Amphiphiles and fatty acids driven primarily by anion−π interactions. The Peptide sequences investigated were functionalized with a perfluorinated phenylalanine residue to promote anion−π interactions with carboxylate headgroups in fatty acids. These interactions were verified here by NMR and circular dichroism experiments as well as investigated using atomistic simulations. Positioning the aromatic units close to the N-terminus of the Peptide backbone near the hydrophobic core of cylindrical nanofibers leads to strong anion−π interactions between both components. With a low content of dodecanoic acid in this position, the cylindrical morphology is preserved. However, as the aromatic units are moved along the Peptide backbone away from the hydrophobic core, the interactions with dodecanoic acid tra...

  • a tenascin c mimetic Peptide amphiphile nanofiber gel promotes neurite outgrowth and cell migration of neurosphere derived cells
    Acta Biomaterialia, 2016
    Co-Authors: Eric J Berns, Zaida Alvarez, Joshua E Goldberger, Job Boekhoven, John A Kessler, Georg H Kuhn, Samuel I. Stupp
    Abstract:

    Abstract Biomimetic materials that display natural bioactive signals derived from extracellular matrix molecules like laminin and fibronectin hold promise for promoting regeneration of the nervous system. In this work, we investigated a biomimetic Peptide amphiphile (PA) presenting a Peptide derived from the extracellular glycoprotein tenascin-C, known to promote neurite outgrowth through interaction with β1 integrin. The tenascin-C mimetic PA (TN-C PA) was found to self-assemble into supramolecular nanofibers and was incorporated through co-assembly into PA gels formed by highly aligned nanofibers. TN-C PA content in these gels increased the length and number of neurites produced from neurons differentiated from encapsulated P19 cells. Furthermore, gels containing TN-C PA were found to increase migration of cells out of neurospheres cultured on gel coatings. These bioactive gels could serve as artificial matrix therapies in regions of neuronal loss to guide neural stem cells and promote through biochemical cues neurite extension after differentiation. One example of an important target would be their use as biomaterial therapies in spinal cord injury. Statement of Significance Tenascin-C is an important extracellular matrix molecule in the nervous system and has been shown to play a role in regenerating the spinal cord after injury and guiding neural progenitor cells during brain development, however, minimal research has been reported exploring the use of biomimetic biomaterials of tenascin-C. In this work, we describe a selfassembling biomaterial system in which Peptide Amphiphiles present a Peptide derived from tenascin-C that promotes neurite outgrowth. Encapsulation of neurons in hydrogels of aligned nanofibers formed by tenascin-C-mimetic Peptide Amphiphiles resulted in enhanced neurite outgrowth. Additionally, these Peptide Amphiphiles promoted migration of neural progenitor cells cultured on nanofiber coatings. Tenascin-C biomimetic biomaterials such as the one described here have significant potential in neuroregenerative medicine.

Matthew Tirrell - One of the best experts on this subject based on the ideXlab platform.

  • cathepsin mediated cleavage of Peptides from Peptide Amphiphiles leads to enhanced intracellular Peptide accumulation
    Bioconjugate Chemistry, 2017
    Co-Authors: Handan Acar, Matthew Tirrell, Ravand Samaeekia, Matthew R Schnorenberg, Dibyendu Kumar Sasmal, Jun Huang, James L Labelle
    Abstract:

    Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein–protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional Peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide Amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive Peptides. PAs consisting of biofunctional Peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent Peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are two major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory Peptide is cleaved from its lip...

  • cathepsin cleavable bim bh3 Peptide Amphiphiles are potent inducers of cellular apoptosis
    Blood, 2015
    Co-Authors: Joseph Bellairs, Matthew Tirrell, Ravand Samaeekia, Handan Acar, James L Labelle
    Abstract:

    The BCL-2 family of proteins forms a complex interaction network that regulates cellular life and death decisions and contributes to cancer development, maintenance, and chemoresistance. BH3 only member proteins (e.g. BIM) serve as cellular stress sentinels and, when triggered, signal irreversible activation of apoptosis through their α-helical BH3 death domains. These pro-apoptotic signals are normally held in check by the multidomain anti-apoptotic proteins (e.g. BCL-XL, MCL-1) but when they are unable to do so the multidomain pro-apoptotic proteins BAX and BAK induce cell death through pore formation in the mitochondrial outer membrane. Therapeutic manipulation of the BCL-2 family with BH3 mimetics (including small molecules and synthetic Peptides) is an emerging paradigm in cancer treatment and immune modulation. The design of next-generation therapeutics based on the BIM BH3 helix offers the unique advantage of recapitulating BIM9s natural capacity to directly target the full complement of anti- and pro-apoptotic BCL-2 proteins. Here, we utilize the highly active BH3 domain of BIM as part of a Peptide amphiphile nanostructure designed to overcome malignant cell death blockade. Peptide Amphiphiles consist of bioactive Peptides linked to hydrophobic lipid-like tail groups. In aqueous solutions, Amphiphiles spontaneously assemble into micelles. Micelle-based Peptide delivery provides several advantages: single micelles deliver high concentration of Peptides into cells, they stabilize Peptide secondary structure(s), and they have the potential for combinatorial synthesis using multiple bioactive moieties targeting non-redundant cell death escape pathways. While the exact mechanism behind cellular uptake of Peptide Amphiphiles remains controversial, recent work has shown that Peptide Amphiphiles intracellularly traffic through lysosomes and endosomes. In order to prevent the bioactive Peptides from being sequestered within these structures, a system of escape is needed. Lysosomes contain many well-characterized proteases, and cathepsin B has previously been utilized to release chemotherapeutics in the context of targetable antibody-based treatments. Here, we generate Peptide Amphiphiles with BIM BH3 Peptides and show that these nanostructures are able to specifically bind recombinant BCL-2 proteins, are stable at physiologic temperatures and pH, quickly enter into cells, and induce dose-responsive apoptosis in malignant hematologic cancers as measured by viability and caspase 3/7 activation. We further demonstrate that incorporating a cathepsin B-cleavable linker between the BIM BH3 Peptide and the hydrophobic tail within individual Amphiphiles results in increased binding to recombinant BCL-2 proteins while also allowing for increased cellular uptake and mitochondrial localization leading to faster and more potent dose-dependent cytotoxicity and caspase activation in malignant cells. Thus, we have developed a modular and potentially targetable nanostructure that represents a new promising strategy for BCL-2 family modulation and apoptosis induction in cancer. Disclosures No relevant conflicts of interest to declare.

  • The Non-Peptidic Part Determines the Internalization Mechanism and Intracellular Trafficking of Peptide Amphiphiles
    PLOS ONE, 2013
    Co-Authors: Dimitris Missirlis, Matthew Black, Tambet Teesalu, Matthew Tirrell
    Abstract:

    Background Peptide Amphiphiles (PAs) are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications.

  • a novel preparative method of silica nanotubes by utilizing self assembly and disassembly of Peptide Amphiphiles
    Chemistry Letters, 2012
    Co-Authors: Tomoko Shimada, Matthew Tirrell, Yasuhiro Tamura, Kazuyuki Kuroda
    Abstract:

    The addition of 2,2,2-trifluoroethanol (TFE) induces both the transition from β-sheet to α-helix structure of Peptides and disassembly of wormlike micelles of Peptide Amphiphiles. The hierarchical ...

  • 4 415 surface engineering using Peptide Amphiphiles
    Comprehensive Biomaterials, 2011
    Co-Authors: Matthew Tirrell
    Abstract:

    Synthetic nanostructures (e.g., polymers, micelles, liposomes, nanoparticles) have great utility as theranostic agents. Regarding clinical implications, synthetic biomaterials have exhibited exceptional stability as bone and dental replacements while offering a platform of nanomaterials with tunable functions allowing the facile tagging of cellular components. Bioactive dressings incorporating polymeric and inorganic composites have shown to be effective in stopping arterial bleeding. The positive aspect of decreased mortality rate because of medical advancements has unfortunately led to an increased need for technological innovations that can sustain and promote biomedical reconstruction after traumatic injuries (e.g., spinal cord injury) and diagnose and treat diseases (e.g., cancer, neurological disorders) over multiple time domains. Biomaterials developed for such applications will benefit from well-defined structures and subdomains. Peptide Amphiphiles (PA) are molecular synthetic building blocks that self-assemble into multidimensional structures such as spherical liposomes and fibrous micelles with well-characterized physicochemical properties. A PA is built using a hydrophilic Peptide head group and a hydrophobic lipid tail subcomponent. The development of PA-based surface-engineering systems involves two-dimensional (2D) surfaces and 3D high-aspect-ratio materials during the past few decades. We cover historical aspects of PA research, present recent examples focusing on biomedical applications, and close with a summary and future directions.

Gregg B Fields - One of the best experts on this subject based on the ideXlab platform.

  • Relating Peptide presentation and biological response through supported films of Peptide Amphiphiles
    Peptides for the New Millennium, 2020
    Co-Authors: Sarah E. Ochsenhirt, Gregg B Fields, Angela K. Dillow, Effrosini Kokkoli, James B. Mccarthy, M. Tirrell
    Abstract:

    The focus of this project is to understand how the secondary structure of a Peptide ligand influences cell behavior. Accordingly, model surfaces upon which the surface density, organization, and presentation of the Peptide can be controlled are required. To accomplish this, we synthesized a series of Peptide Amphiphiles (Fig. 1) that have hydrocarbon tails and head groups that contain RGD (Arg-Gly-Asp) or GRGDSP (Gly-Arg-Gly-Asp-SerPro) Peptides [1]. The versatility of this protocol allows several variations of these adhesive Peptide Amphiphiles to be synthesized. The Peptide may be linear or cyclic and may be attached to the hydrocarbon tails at either the N-terminus or both Nand C-termini. These Peptide Amphiphiles are synthesized in order to produce thin films for surface modifications. The Peptide Amphiphiles are ordered at the air-water interface, and their assembly analyzed with Langmuir isotherms and, when applicable, by Fourier transform infrared spectroscopy (FTIR). Using the Langmuir-Blodgett technique, a condensed monolayer of the RGD Amphiphiles is deposited onto a hydrophobic substrate using a downstroke. The Langmuir-Blodgett technique has been selected because the resultant film presents the Peptide uniformly at the interface. We control the surface density of the Peptide and manipulate the spatial organization of the monolayer by mixing the Peptide amphiphile with an inert background amphiphile. The bioactive film is then used as the substrate for short term (1 h) adhesion assays involving human umbilical vein endothelial cells (HUVECs) or M14#5 human melanoma cells. The adhesive activity of the Peptide Amphiphiles is evaluated by measuring the size and shape of the cells after they have been fixed and stained.

  • characterization of Peptide Amphiphiles possessing cellular activation sequences
    Biomacromolecules, 2003
    Co-Authors: Navdeep B Malkar, Janelle L Lauerfields, Darius Juska, Gregg B Fields
    Abstract:

    Numerous approaches have been described for modifying biomaterials to incorporate extracellular matrix components. “Peptide−Amphiphiles”, whereby monoalkyl hydrocarbon chains are covalently linked ...

  • adhesion of α5β1 receptors to biomimetic substrates constructed from Peptide Amphiphiles
    Biomaterials, 2001
    Co-Authors: Angela K. Dillow, Sarah E. Ochsenhirt, Gregg B Fields, James B. Mccarthy, Matthew Tirrell
    Abstract:

    Abstract Biomimetic membrane surfaces functionalized with fragments of the extracellular matrix protein, fibronectin, are constructed from mixtures of Peptide and polyethylene glycol (PEG) Amphiphiles. Peptides from the primary binding loop, GRGDSP, were used in conjunction with the synergy site Peptide, PHSRN, in the III9–10 sites of human fibronectin. These Peptides were attached to dialkyl lipid tails to form Peptide Amphiphiles. PEG Amphiphiles were mixed in the layer to minimize non-specific adhesion in the background. GRGDSP and PEG Amphiphiles or GRGDSP, PHSRN, and PEG Amphiphiles were mixed in various ratios and deposited on solid substrates from the air–water interface using Langmuir–Blodgett techniques. In this method, Peptide composition, density, and presentation could be controlled accurately. The effectiveness of these substrates to mimic native fibronectin is evaluated by their ability to generate adhesive forces when they are in contact with purified activated α5β1 integrin receptors that are immobilized on an opposing surface. Adhesion is measured using a contact mechanical approach (JKR experiment). The effects of membrane composition, density, temperature, and Peptide conformation on adhesion to activated integrins in this simulated cell adhesion setup were determined. Addition of the synergy site, PHSRN, was found to increase adhesion of α5β1 to biomimetic substrates markedly. Increased Peptide mobility (due to increased experimental temperature) increased integrin adhesion markedly at low Peptide concentrations. A balance between Peptide density and steric accessibility of the receptor binding face to α5β1 integrin was required for highest adhesion.

  • cellular recognition of synthetic Peptide Amphiphiles in self assembled monolayer films
    Biomaterials, 1999
    Co-Authors: Teika Pakalns, Gregg B Fields, James B. Mccarthy, Kraig Haverstick, Daniel L Mooradian, Matthew Tirrell
    Abstract:

    The incorporation of lipidated cell adhesion Peptides into self-assembled structures such as films provides the opportunity to develop unique biomimetic materials with well-organized interfaces. Synthetic dialkyl tails have been linked to the amino-terminus, carboxyl-terminus, and both termini of the cell recognition sequence Arg–Gly–Asp (RGD) to produce amino-coupled, carboxyl-coupled, and looped RGD Peptide Amphiphiles. All three amphiphilic RGD versions self-assembled into fairly stable mixed monolayers that deposited well as Langmuir–Blodgett films on surfaces, except for films containing amino-coupled RGD Amphiphiles at high Peptide concentrations. FT-IR studies showed that amino-coupled RGD head groups formed the strongest lateral hydrogen bonds. Melanoma cells spread on looped RGD Amphiphiles in a concentration-dependent manner, spread indiscriminately on carboxyl-coupled RGD Amphiphiles, and did not spread on amino-coupled RGD Amphiphiles. Looped RGD Amphiphiles promoted the adhesion, spreading, and cytoskeletal reorganization of melanoma and endothelial cells while control looped Arg–Gly–Glu (RGE) Amphiphiles inhibited them. Antibody inhibition of the integrin receptor α3β1 blocked melanoma cell adhesion to looped RGD Amphiphiles. These results confirm that novel biomolecular materials containing synthetic Peptide Amphiphiles have the potential to control cellular behavior in a specific manner.

  • Structure and Dynamics of Peptide−Amphiphiles Incorporating Triple-Helical Proteinlike Molecular Architecture†
    Biochemistry, 1999
    Co-Authors: Ying Ching Yu, Kevin H Mayo, Matthew Tirrell, Vikram Roontga, Vladimir A Daragan, Gregg B Fields
    Abstract:

    Organized polymeric assemblies that incorporate bioactive sequences and structures are finding important applications for the study of protein structure−function relationships. We have recently described a heteropolymeric Peptide−amphiphile system that forms organized structures in solution and on surfaces. While the overall three-dimensional features of Peptide−Amphiphiles have been studied previously, the precise environment of specific residues, particularly those within biologically active regions, have not been examined in detail. In the present study, we have used heteronuclear single quantum coherence (HSQC) and inverse-detected 1H−15N NMR spectroscopy to examine the structure and dynamics of a Peptide and Peptide−amphiphile that incorporate the α1(IV)1263−1277 ([IV-H1]) amino acid sequence from type IV collagen. Three variants of the sequence (Gly-Pro-Hyp)4-[IV-H1]-(Gly-Pro-Hyp)4 were constructed with a single 15N-labeled Gly placed in the middle of the N-terminal (Gly-Pro-Hyp)4 region (residue Gl...

Hung D Nguyen - One of the best experts on this subject based on the ideXlab platform.

  • sequence dependent structural stability of self assembled cylindrical nanofibers by Peptide Amphiphiles
    Biomacromolecules, 2015
    Co-Authors: Iris W Fu, Hung D Nguyen
    Abstract:

    Three-dimensional networks of nanofibers, which are formed through self-assembly of Peptide Amphiphiles, serve as a biomimetic hydrogel scaffold for tissue engineering. With an emphasis to improve hydrogel properties for cell-specific behavior, a better understanding between structural characteristics and physical properties of the macroscopic gel is sought. Large-scale molecular dynamics simulations were performed on two PA sequences with identical composition (palmitoyl-V3A3E3 and palmitoyl-A3V3E3) showing different self-assembly kinetic mechanisms. While both sequences yielded cylindrical nanofibers, these structures have contrasting internal arrangement with respect to the hydrophobic core; the former is continuous with predominately alkyl tails, whereas the latter is disjointed with interconnecting micelles. Two additional sequences (palmitoyl-V6E3 and palmitoyl-A6E3) were examined to determine the effects of a homogeneous β-sheet forming segment that is either strongly or mildly hydrophobic on self-...

  • solvent effects on kinetic mechanisms of self assembly by Peptide Amphiphiles via molecular dynamics simulations
    Langmuir, 2015
    Co-Authors: Iris W Fu, Cade B Markegard, Hung D Nguyen
    Abstract:

    Peptide Amphiphiles are known to form a variety of distinctive self-assembled nanostructures (including cylindrical nanofibers in hydrogels) dependent upon the solvent conditions. Using a novel coarse-grained model, large-scale molecular dynamics simulations are performed on a system of 800 Peptide Amphiphiles (sequence, palmitoyl-Val3Ala3Glu3) to elucidate kinetic mechanisms of molecular assembly as a function of the solvent conditions. The assembly process is found to occur via a multistep process with transient intermediates that ultimately leads to the stabilized nanostructures including open networks of β-sheets, cylindrical nanofibers, and elongated micelles. Different kinetic mechanisms are compared in terms of Peptide secondary structures, solvent-accessible surface area, radius of gyration, relative shape anisotropy, intra/intermolecular interactions, and aggregate size dynamics to provide insightful information for the design of functional biomaterials.

  • A Tail of Two Peptide Amphiphiles: Effect of Conjugation with Hydrophobic Polymer on Folding of Peptide Sequences
    Biomacromolecules, 2014
    Co-Authors: Iris W Fu, Cade B Markegard, Seong E. Choi, Hung D Nguyen
    Abstract:

    Peptide Amphiphiles (PA) offer the potential of incorporating biological function into synthetic materials for tissue engineering in regenerative medicine. These hybrid conjugates are known to undergo self-assembly starting from single molecules to nanofibers before turning into hydrogel scaffolds—such a process involves conformational changes in secondary structures of Peptides. Therefore, insights on the ability of Peptide Amphiphiles to form secondary structure as single molecules are useful for understanding self-assembly behavior. We report here a molecular simulation study of Peptide folding by two PA sequences, each contains an alkyl tail and short Peptide segment. The alkyl tail is observed to play two opposing roles in modulating sequence-dependent folding kinetics and thermodynamics. On one hand, it restricts conformational freedom reducing the entropic cost of folding, which is thus promoted. On the other hand, it acts as an interaction site with nonpolar Peptide residues, blocking the Peptide ...

  • mechanism of the ph controlled self assembly of nanofibers from Peptide Amphiphiles
    Journal of Physical Chemistry C, 2014
    Co-Authors: Yoann Cote, Joshua E Goldberger, Iris W Fu, Hung D Nguyen, Eric T Dobson, Jana K Shen
    Abstract:

    Stimuli-responsive, self-assembling nanomaterials hold a great promise to revolutionize medicine and technology. However, current discovery is slow and often serendipitous. Here we report a multiscale modeling study to elucidate the pH-controlled self-assembly of nanofibers from the Peptide Amphiphiles, palmitoyl-I-A3E4-NH2. The coarse-grained simulations revealed the formation of random-coil based spherical micelles at strong electrostatic repulsion. However, at weak or no electrostatic repulsion, the micelles merge into a nanofiber driven by the β-sheet formation between the Peptide segments. The all-atom constant pH molecular dynamics revealed a cooperative transition between random coil and β-sheet in the pH range 6–7, matching the CD data. Interestingly, although the bulk pKa is more than one unit below the transition pH, consistent with the titration data, the highest pKa’s coincide with the transition pH, suggesting that the latter may be tuned by modulating the pKa’s of a few solvent-buried Glu si...

  • role of hydrophobicity on self assembly by Peptide Amphiphiles via molecular dynamics simulations
    Langmuir, 2014
    Co-Authors: Iris W Fu, Cade B Markegard, Hung D Nguyen
    Abstract:

    Using a novel coarse-grained model, large-scale molecular dynamics simulations were performed to examine self-assembly of 800 Peptide Amphiphiles (sequence palmitoyl-V3A3E3). Under suitable physiological conditions, these molecules readily assemble into nanofibers leading to hydrogel construction as observed in experiments. Our simulations capture this spontaneous self-assembly process, including formation of secondary structure, to identify morphological transitions of distinctive nanostructures. As the hydrophobic interaction is increased, progression from open networks of secondary structures toward closed cylindrical nanostructures containing either β-sheets or random coils are observed. Moreover, temperature effects are also determined to play an important role in regulating formation of secondary structures within those nanostructures. These understandings of the molecular interactions involved and the role of environmental factors on hydrogel formation provide useful insight for development of inno...

Iris W Fu - One of the best experts on this subject based on the ideXlab platform.

  • sequence dependent structural stability of self assembled cylindrical nanofibers by Peptide Amphiphiles
    Biomacromolecules, 2015
    Co-Authors: Iris W Fu, Hung D Nguyen
    Abstract:

    Three-dimensional networks of nanofibers, which are formed through self-assembly of Peptide Amphiphiles, serve as a biomimetic hydrogel scaffold for tissue engineering. With an emphasis to improve hydrogel properties for cell-specific behavior, a better understanding between structural characteristics and physical properties of the macroscopic gel is sought. Large-scale molecular dynamics simulations were performed on two PA sequences with identical composition (palmitoyl-V3A3E3 and palmitoyl-A3V3E3) showing different self-assembly kinetic mechanisms. While both sequences yielded cylindrical nanofibers, these structures have contrasting internal arrangement with respect to the hydrophobic core; the former is continuous with predominately alkyl tails, whereas the latter is disjointed with interconnecting micelles. Two additional sequences (palmitoyl-V6E3 and palmitoyl-A6E3) were examined to determine the effects of a homogeneous β-sheet forming segment that is either strongly or mildly hydrophobic on self-...

  • solvent effects on kinetic mechanisms of self assembly by Peptide Amphiphiles via molecular dynamics simulations
    Langmuir, 2015
    Co-Authors: Iris W Fu, Cade B Markegard, Hung D Nguyen
    Abstract:

    Peptide Amphiphiles are known to form a variety of distinctive self-assembled nanostructures (including cylindrical nanofibers in hydrogels) dependent upon the solvent conditions. Using a novel coarse-grained model, large-scale molecular dynamics simulations are performed on a system of 800 Peptide Amphiphiles (sequence, palmitoyl-Val3Ala3Glu3) to elucidate kinetic mechanisms of molecular assembly as a function of the solvent conditions. The assembly process is found to occur via a multistep process with transient intermediates that ultimately leads to the stabilized nanostructures including open networks of β-sheets, cylindrical nanofibers, and elongated micelles. Different kinetic mechanisms are compared in terms of Peptide secondary structures, solvent-accessible surface area, radius of gyration, relative shape anisotropy, intra/intermolecular interactions, and aggregate size dynamics to provide insightful information for the design of functional biomaterials.

  • A Tail of Two Peptide Amphiphiles: Effect of Conjugation with Hydrophobic Polymer on Folding of Peptide Sequences
    Biomacromolecules, 2014
    Co-Authors: Iris W Fu, Cade B Markegard, Seong E. Choi, Hung D Nguyen
    Abstract:

    Peptide Amphiphiles (PA) offer the potential of incorporating biological function into synthetic materials for tissue engineering in regenerative medicine. These hybrid conjugates are known to undergo self-assembly starting from single molecules to nanofibers before turning into hydrogel scaffolds—such a process involves conformational changes in secondary structures of Peptides. Therefore, insights on the ability of Peptide Amphiphiles to form secondary structure as single molecules are useful for understanding self-assembly behavior. We report here a molecular simulation study of Peptide folding by two PA sequences, each contains an alkyl tail and short Peptide segment. The alkyl tail is observed to play two opposing roles in modulating sequence-dependent folding kinetics and thermodynamics. On one hand, it restricts conformational freedom reducing the entropic cost of folding, which is thus promoted. On the other hand, it acts as an interaction site with nonpolar Peptide residues, blocking the Peptide ...

  • mechanism of the ph controlled self assembly of nanofibers from Peptide Amphiphiles
    Journal of Physical Chemistry C, 2014
    Co-Authors: Yoann Cote, Joshua E Goldberger, Iris W Fu, Hung D Nguyen, Eric T Dobson, Jana K Shen
    Abstract:

    Stimuli-responsive, self-assembling nanomaterials hold a great promise to revolutionize medicine and technology. However, current discovery is slow and often serendipitous. Here we report a multiscale modeling study to elucidate the pH-controlled self-assembly of nanofibers from the Peptide Amphiphiles, palmitoyl-I-A3E4-NH2. The coarse-grained simulations revealed the formation of random-coil based spherical micelles at strong electrostatic repulsion. However, at weak or no electrostatic repulsion, the micelles merge into a nanofiber driven by the β-sheet formation between the Peptide segments. The all-atom constant pH molecular dynamics revealed a cooperative transition between random coil and β-sheet in the pH range 6–7, matching the CD data. Interestingly, although the bulk pKa is more than one unit below the transition pH, consistent with the titration data, the highest pKa’s coincide with the transition pH, suggesting that the latter may be tuned by modulating the pKa’s of a few solvent-buried Glu si...

  • role of hydrophobicity on self assembly by Peptide Amphiphiles via molecular dynamics simulations
    Langmuir, 2014
    Co-Authors: Iris W Fu, Cade B Markegard, Hung D Nguyen
    Abstract:

    Using a novel coarse-grained model, large-scale molecular dynamics simulations were performed to examine self-assembly of 800 Peptide Amphiphiles (sequence palmitoyl-V3A3E3). Under suitable physiological conditions, these molecules readily assemble into nanofibers leading to hydrogel construction as observed in experiments. Our simulations capture this spontaneous self-assembly process, including formation of secondary structure, to identify morphological transitions of distinctive nanostructures. As the hydrophobic interaction is increased, progression from open networks of secondary structures toward closed cylindrical nanostructures containing either β-sheets or random coils are observed. Moreover, temperature effects are also determined to play an important role in regulating formation of secondary structures within those nanostructures. These understandings of the molecular interactions involved and the role of environmental factors on hydrogel formation provide useful insight for development of inno...