Phase Diagram for Assembly of Biologically-Active Peptide Amphiphiles

Tsonchev, Stefan; Niece, Krista L.; Schatz, George C.; Ratner, Mark A.; Stupp, Samuel I.

doi:10.1021/jp076273z

Cited by 74 publications

(61 citation statements)

References 43 publications

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“…Furthermore, a comprehensive phase diagram showing the variation of micellar structures that can be formed when balancing the strength of hydrophobic and hydrogen-bonding interactions perpendicular to the PA axis was characterized by Velichko et al 49 In these studies, Velichko et al used a united atom model with directional hydrogen-bonding to describe the peptide amphiphiles, and showed that the shape of self-assemblies can range from spherical micelles to single β -sheets to elongated cylindrical fibers. 49, 50 Following, there have been a multitude of atomistic and coarse-grained MD simulations studies analysing the structure and self-assembly pathways of PA fibers 5, 45, 48, 51–64 .…”

Section: Introductionmentioning

confidence: 99%

Coarse-grained molecular dynamics studies of the structure and stability of peptide-based drug amphiphile filaments

2017

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Peptide-based supramolecular filaments, in particular filaments self-assembled by drug amphiphiles (DAs), possess great potential in the field of drug delivery. These filaments possess one hundred percent drug loading, with a release mechanism that can be tuned based on the dissociation of the supramolecular filaments and the degradation of the DAs [Cheetham et al., J. Am. Chem. Soc. 135 (8), 2907 (2013)]. Recently, much attention has been drawn to the competing intermolecular interactions that drive the self-assembly of peptide-based amphiphiles into supramolecular filaments. Recently, we reported on long-time atomistic molecular dynamics simulations to characterize the structure and growth of chiral filaments by the self-assembly of a DA containing the aromatic anti-cancer drug camptothecin [Kang et al., Macromolecules 49 (3), 994 (2016)]. We found that the π–π stacking of the aromatic drug governs the early stages of the self-assembly process, while also contributing towards the chirality of the self-assembled filament. Based on these all-atomistic simulations, we now build a chemically accurate coarse-grained model that can capture the structure and stability of these supramolecular filaments at long time-scales (microseconds). These coarse-grained models successfully recapitulate the growth of the molecular clusters (and their elongation trends) compared with previously reported atomistic simulations. Furthermore, the interfacial structure and the helicity of the filaments are conserved. Next, we focus on characterization of the disassembly process of a 0.675 μm DA filament at microsecond time-scales. These results provide very useful tools for the rational design of functional supramolecular filaments, in particular supramolecular filaments for drug delivery applications.

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Section: Introductionmentioning

confidence: 99%

Coarse-grained molecular dynamics studies of the structure and stability of peptide-based drug amphiphile filaments

2017

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“…Although the results are comparable to experimental findings12, 13 by capturing the detailed interactions and distinctive structural motifs that comprise of a cylindrical nanofiber, the mechanism by which this structure is formed cannot be extracted since the simulation started from a cylindrical template. Consequently, most simulation studies capable of examining the whole self‐assembly process have been limited to using simplified models 30–33. For instance, Velichko et al used a coarse‐grained model to perform Monte Carlo simulations providing a molecular perspective between the structure and simulation conditions of the system 32.…”

Section: Introductionmentioning

confidence: 99%

The Role of Electrostatics and Temperature on Morphological Transitions of Hydrogel Nanostructures Self‐Assembled by Peptide Amphiphiles Via Molecular Dynamics Simulations

Markegard

Chu

et al. 2013

Adv Healthcare Materials

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Smart biomaterials that are self-assembled from peptide amphiphiles (PA) are known to undergo morphological transitions in response to specific physiological stimuli. The design of such customizable hydrogels is of significant interest due to their potential applications in tissue engineering, biomedical imaging, and drug delivery. Using a novel coarse-grained peptide/polymer model, which has been validated by comparison of equilibrium conformations from atomistic simulations, large-scale molecular dynamics simulations are performed to examine the spontaneous self-assembly process. Starting from initial random configurations, these simulations result in the formation of nanostructures of various sizes and shapes as a function of the electrostatics and temperature. At optimal conditions, the self-assembly mechanism for the formation of cylindrical nanofibers is deciphered involving a series of steps: (1) PA molecules quickly undergo micellization whose driving force is the hydrophobic interactions between alkyl tails; (2) neighboring peptide residues within a micelle engage in a slow ordering process that leads to the formation of β-sheets exposing the hydrophobic core; (3) spherical micelles merge together through an end-to-end mechanism to form cylindrical nanofibers that exhibit high structural fidelity to the proposed structure based on experimental data. As the temperature and electrostatics vary, PA molecules undergo alternative kinetic mechanisms, resulting in the formation of a wide spectrum of nanostructures. A phase diagram in the electrostatics-temperature plane is constructed delineating regions of morphological transitions in response to external stimuli.

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“…Whether the studies focus on method development, [32][33][34][35][36][37] the roles of various intermolecular interactions, [38,39] or predictions for specific systems, [40][41][42] it is clear that simulations of molecular self-assembly are difficult. For one, the underlying physics of aggregation often spans numerous length and time scales.…”

Section: Local Ordermentioning

confidence: 99%

Emergent Properties in Locally Ordered Molecular Materials

Jackson

Savoie

Reuter

et al. 2014

Israel Journal of Chemistry

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The two classic structural classifications of solid matter, crystalline and amorphous, are quite useful for inorganic solids, from antimony trichloride to zinc dibromide and beyond. However, for many molecular materials, especially those based on components containing ten or more non‐hydrogen atoms, ordered single crystals are less common, and intermediate structures that are neither amorphous nor crystalline frequently dominate. Herein, we discuss several situations in which there is local (or partial) ordering in such molecular materials. These materials go beyond the standard concepts concerning polymers and must account for imperfect but substantial local ordering, such as that caused by weak intermolecular interactions (e.g., π stacking, H‐bonding, and/or dispersion forces). This local ordering has important implications for, and applications in, materials properties: we specifically consider dielectric response, electron transport, and exciton transfer. Finally, we discuss the fundamental importance of the effective dimensionality of partially ordered domains in molecular materials.

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Phase Diagram for Assembly of Biologically-Active Peptide Amphiphiles

Cited by 74 publications

References 43 publications

Coarse-grained molecular dynamics studies of the structure and stability of peptide-based drug amphiphile filaments

Coarse-grained molecular dynamics studies of the structure and stability of peptide-based drug amphiphile filaments

The Role of Electrostatics and Temperature on Morphological Transitions of Hydrogel Nanostructures Self‐Assembled by Peptide Amphiphiles Via Molecular Dynamics Simulations

Emergent Properties in Locally Ordered Molecular Materials

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