In situ real-time monitoring of the mechanism of self-assembly of short peptide supramolecular polymers
12 Jul 2021-Materials Chemistry Frontiers (Royal Society of Chemistry)-Vol. 5, Iss: 14, pp 5452-5462
TL;DR: In this paper, the early stages of the fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF) self-assembly process with single-molecule resolution, the kinetics of fiber formation, the packaging of peptides within the fibers and the capacity of the peptides to reassemble after disruption (self-healing) in the presence of different metallic cations.
Abstract: Making use of the combination of multiparametric Fluorescence Lifetime Imaging Microscopy (FLIM) and single-molecule Fluorescence Lifetime Correlation Spectroscopy (FLCS), we have been able to study for the early stages of the fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF) self-assembly process with single-molecule resolution, the kinetics of fiber formation, the packaging of the peptides within the fibers and the capacity of the peptides to reassemble after disruption (self-healing) in the presence of different metallic cations. Other techniques such as FTIR, TEM, DSC and DFT calculations support our findings. The impact that the mechanism of self-assembly has on the physical (rigidity and self-healing) properties of the resulting gels have also been evaluated by rheology. Calcium ions are able to promote the self-assembly of Fmoc-FF faster and more efficiently, forming more rigid hydrogels than do cesium ions. The reasons behind this effect may be explained by the different capacities that these two cations have to coordinate with the peptide, modulate its hydrophobicity and stabilize the water–solute interphase. These findings shed light on the impact that small changes have on the process of self-assembly and can help to understand the influence of the environmental conditions on the in vivo uncontrolled self-assembly of certain proteins.
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TL;DR: In this paper, the authors discuss the mechanism for these phenomena within an adapted version of the two-state Muller-Lee-Graziano model for water, which provides a complete description of the ternary water/cosolvent/solute system for small solute particles.
Abstract: Kosmotropic cosolvents added to an aqueous solution promote the aggregation of hydrophobic solute particles, while chaotropic cosolvents act to destabilise such aggregates. We discuss the mechanism for these phenomena within an adapted version of the two-state Muller-Lee-Graziano model for water, which provides a complete description of the ternary water/cosolvent/solute system for small solute particles. This model contains the dominant effect of a kosmotropic substance, which is to enhance the formation of water structure. The consequent preferential exclusion both of cosolvent molecules from the solvation shell of hydrophobic particles and of these particles from the solution leads to a stabilisation of aggregates. By contrast, chaotropic substances disrupt the formation of water structure, are themselves preferentially excluded from the solution, and thereby contribute to solvation of hydrophobic particles. We use Monte Carlo simulations to demonstrate at the molecular level the preferential exclusion or binding of cosolvent molecules in the solvation shell of hydrophobic particles, and the consequent enhancement or suppression of aggregate formation. We illustrate the influence of structure-changing cosolvents on effective hydrophobic interactions by modelling qualitatively the kosmotropic effect of sodium chloride and the chaotropic effect of urea.
146 citations
TL;DR: In this article, the authors investigated the co-aggregation of different aromatic short peptides containing Fmoc- (fluorenylmethyloxycarbonyl-) and Nap- (2-(naphthalen-2-yloxy)acetyl) groups having also different chirality.
9 citations
TL;DR: In this article , a substitution on the aromatic side-chain of phenylalanine with either fluorine or iodine enables supramolecular diversity upon self-assembly at neutral pH, leading to hydrogels or crystals.
Abstract: Dipeptides are popular building blocks for supramolecular gels that do not persist in the environment and may find various applications. In this work, we show that a simple substitution on the aromatic side-chain of phenylalanine with either fluorine or iodine enables supramolecular diversity upon self-assembly at neutral pH, leading to hydrogels or crystals. Each building block is characterized by 1H- and 13C-NMR spectroscopy, LC-MS, circular dichroism, and molecular models. The supramolecular behaviour is monitored with a variety of techniques, including circular dichroism, oscillatory rheology, transmission electron microscopy, attenuated total reflectance Fourier-transformed infrared spectroscopy, visible Raman spectroscopy, synchrotron-radiation single-crystal X-ray diffraction and UV Resonance Raman spectroscopy, allowing key differences to be pinpointed amongst the halogenated analogues.
6 citations
TL;DR: Self-assembled peptides and proteins have turned out to be excellent templates for the growth of inorganic minerals trying to emulate natural biomineralization processes as mentioned in this paper , and researchers have developed complex sophisticate...
Abstract: Self-assembled peptides and proteins have turned out to be excellent templates for the growth of inorganic minerals trying to emulate natural biomineralization processes. Doing this, researchers have developed complex sophisticate...
6 citations
TL;DR: D-Phe-L-Val is the first heterochiral dipeptide to self-assemble into supramolecular water-channels whose cavity is defined by four peptide molecules arranged head-to-tail, and it displays excellent biocompatibility in vitro.
Abstract: Dipeptides are convenient building blocks for supramolecular gel biomaterials that can be produced on a large scale at low cost and do not persist in the environment. In the case of unprotected sequences, hydrophobicity is a key requirement to enable gelation, with Phe-Phe standing out for its self-assembling ability. Conversely, more hydrophilic sequences such as homochiral dipeptides Phe-Val and Val-Phe neither fibrillate nor gel aqueous buffers and their crystal structures reveal amphipathic layers. In this work, we test emerging rules for the design of self-assembling dipeptides using heterochiral Phe-Val and Val-Phe. Each dipeptide is characterized by 1H- and 13C-NMR, LC-MS, circular dichroism, infrared and Raman spectroscopies, rheology, electron microscopy, and single-crystal X-ray diffraction. In particular, D-Phe-L-Val is the first heterochiral dipeptide to self-assemble into supramolecular water-channels whose cavity is defined by four peptide molecules arranged head-to-tail. This minimalistic sequence is devoid of amyloid character as probed by thioflavin T fluorescence and it displays excellent biocompatibility in vitro. The dataset provided, through comparison with the literature, significantly advances the definition of molecular design rules for minimalistic unprotected dipeptides that self-assemble into water-channels and biocompatible gels, to assist with the future development of supramolecular biomaterials with fine control over nanomorphological features for a variety of applications.
6 citations
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26 Nov 1998
TL;DR: In this article, the authors present a comprehensive overview of the properties and properties of complex fluids and their properties in terms of physics, chemistry, physics theory, and physics of complex fluid properties.
Abstract: Part I: Fundamentals 1. Introduction to Complex Fluids 1.3 Rheological Measurements and Properties 1.4 Kinematics and Stress 1.5 Flow, Slip, and Yield 1.6 Structural Probes of Complex Fluids 1.7 Computational Methods 1.8 The Stress Tensor 1.9 Summary 2. Basic Forces 2.1 Intoduction 2.3 Van der Waals Interactions 2.4 Electrostatic Interactions 2.5 Hydrogen-Bonding, Hydrophobic, and Other Interactions 2.6 Summary Part II: Polymers, Glassy Liquids, and Polymer Gels 3. Polymers 3.1 Introduction 3.2 Equilibrium Properties 3.3 Intrinsic Viscosity and Overlap Concentration 3.4 Elementary Molecular Theories 3.5 Linear Viscoelasticity and Time-Temperature Superposition 3.6 The Rheology of Dilute Polymer Solutions 3.7 The Rheology of Entangled Polymers 3.8 Summary 4. Glassy Liquids 4.1 Introduction 4.2 Phenomenology of the Glass Transition 4.3 Free-Volume Theories 4.4 Entropy Theories 4.5 Nonlinear Relaxation and Aging 4.6 Mode-Coupling Theory and Colloidal Hard-Sphere Glasses 4.7 Analog Models 4.8 Rheology of Glassy Liquids 4.9 Summary 5. Polymer Gels 5.1 Introduction 5.2 Gelation Theoies 5.3 Rheology of Chemical Gels and Near-Gels 5.4 Rheology of Physical Gels 5.5 Summary Part III: Suspensions 6. Particulate Suspensions 6.1 Introduction 6.2 Hard, and Slightly Deformable Spheres 6.3 Nonspherical Particles 6.4 Electrically Charged Particles 6.5 Particles in Viscoelastic Liquids: "Filled Melts" 6.6 Summary 7. Particulate Gels 7.1 Introduction 7.2 Particle Interactions in Suspensions 7.3 Rheology of Particulate Gels 7.4 Summary 8. Electro- and Magneto-Responsive Suspensions 8.1 Introduction 8.2 Electrorheological Fluids 8.3 Magnetorheological Fluids 8.4 Ferrofluids 8.5 Summary 9. Foams, Emulsions, and Blends 9.1 Introduction 9.2 Emulsion Preparation 9.3 Rheology of Emulsions and Immiscible Blends 9.4 Structure and Coarsening of Foams 9.5 Rheology of Foams 9.6 Summary Part IV: Liquid Crystals and Self-Assembling Fluids 10. Liquid Crystals 10.1 Introduction 10.2 Nematics 10.3 Cholesterics: Chiral Nemantics 10.4 Smectics 10.5 Summary 11. Liquid Crystalline Polymers 11.1 Introduction 11.2 Molecular Characteristics of Liquid Crystalline Polymers 11.3 Flow Properties of Nematic LCP's 11.4 Molecular Dynamics of Polymeric Nematics 11.5 Molecular Theory for the Rheology of Polymeric Nematics 11.6 Summary 12. Surfactant Solutions 12.1 Introduction 12.2 Methods of Predicting Microstructures 12.3 Disordered Micellar Solutions 12.4 Surfactant Liquid Crystals 12.5 Summary 13. Block Copolymers 13.1 Introduction 13.2 Thermodynamics of Block Copolymers 13.3 Rheology and Shear-Aligning of Block Copolymers 13.4 Summary Appendix: Momentum-Balance Equations in the Absence of Inertia
3,840 citations
TL;DR: Two complementary strategies can be used in the fabrication of molecular biomaterials as discussed by the authors : chemical complementarity and structural compatibility, both of which confer the weak and noncovalent interactions that bind building blocks together during self-assembly.
Abstract: Two complementary strategies can be used in the fabrication of molecular biomaterials. In the 'top-down' approach, biomaterials are generated by stripping down a complex entity into its component parts (for example, paring a virus particle down to its capsid to form a viral cage). This contrasts with the 'bottom-up' approach, in which materials are assembled molecule by molecule (and in some cases even atom by atom) to produce novel supramolecular architectures. The latter approach is likely to become an integral part of nanomaterials manufacture and requires a deep understanding of individual molecular building blocks and their structures, assembly properties and dynamic behaviors. Two key elements in molecular fabrication are chemical complementarity and structural compatibility, both of which confer the weak and noncovalent interactions that bind building blocks together during self-assembly. Using natural processes as a guide, substantial advances have been achieved at the interface of nanomaterials and biology, including the fabrication of nanofiber materials for three-dimensional cell culture and tissue engineering, the assembly of peptide or protein nanotubes and helical ribbons, the creation of living microlenses, the synthesis of metal nanowires on DNA templates, the fabrication of peptide, protein and lipid scaffolds, the assembly of electronic materials by bacterial phage selection, and the use of radiofrequency to regulate molecular behaviors.
3,125 citations
TL;DR: The specific features of supramolecular polymers that can lead to applications in a variety of fields are reviewed, including: materials—in which processability and self-healing properties are of interest; biomedicine— in which the concerns are dynamic functionality and biodegradability; and hierarchical assembly and electronic systems—with an interest in unidirectionality of charge flow.
Abstract: Supramolecular polymers can be random and entangled coils with the mechanical properties of plastics and elastomers, but with great capacity for processability, recycling, and self-healing due to their reversible monomer-to-polymer transitions. At the other extreme, supramolecular polymers can be formed by self-assembly among designed subunits to yield shape-persistent and highly ordered filaments. The use of strong and directional interactions among molecular subunits can achieve not only rich dynamic behavior but also high degrees of internal order that are not known in ordinary polymers. They can resemble, for example, the ordered and dynamic one-dimensional supramolecular assemblies of the cell cytoskeleton and possess useful biological and electronic functions.
2,777 citations
TL;DR: This work presents metallosupramolecular polymers that can be mended through exposure to light, which consist of telechelic, rubbery, low-molecular-mass polymers with ligand end groups that are non-covalently linked through metal-ion binding.
Abstract: Smart materials with an in-built ability to repair damage caused by normal wear and tear could prove useful in a wide range of applications. Most healable polymer-based materials so far developed require heating of the damaged area. But Burnworth et al. have now produced materials — in the form of polymer strands linked through metal complexes — that can be mended through exposure to light. The metal complexes in these materials can absorb ultraviolet light that is then converted into heat, which temporarily unlinks the polymer strands for quick and efficient defect healing. In principle, healing can take place in situ and while under load. Polymers with the ability to repair themselves after sustaining damage could extend the lifetimes of materials used in many applications1. Most approaches to healable materials require heating the damaged area2,3,4. Here we present metallosupramolecular polymers that can be mended through exposure to light. They consist of telechelic, rubbery, low-molecular-mass polymers with ligand end groups that are non-covalently linked through metal-ion binding. On exposure to ultraviolet light, the metal–ligand motifs are electronically excited and the absorbed energy is converted into heat. This causes temporary disengagement of the metal–ligand motifs and a concomitant reversible decrease in the polymers’ molecular mass and viscosity5, thereby allowing quick and efficient defect healing. Light can be applied locally to a damage site, so objects can in principle be healed under load. We anticipate that this approach to healable materials, based on supramolecular polymers and a light–heat conversion step, can be applied to a wide range of supramolecular materials that use different chemistries.
1,476 citations
TL;DR: Because the location of the metastable critical point can be controlled by changing the composition of the solvent, the present work suggests a systematic approach to promote protein crystallization.
Abstract: Numerical simulations of homogeneous crystal nucleation with a model for globular proteins with short-range attractive interactions showed that the presence of a metastable fluid-fluid critical point drastically changes the pathway for the formation of a crystal nucleus. Close to this critical point, the free-energy barrier for crystal nucleation is strongly reduced and hence, the crystal nucleation rate increases by many orders of magnitude. Because the location of the metastable critical point can be controlled by changing the composition of the solvent, the present work suggests a systematic approach to promote protein crystallization.
1,265 citations