Biomimetic temporal self-assembly via fuel-driven controlled supramolecular polymerization (original) (raw)
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Multiscale Molecular Modelling of ATP-fueled Supramolecular Polymerisation and Depolymerisation
2020
Fuel-regulated self-assembly is a key principle by which Nature creates spatiotemporally controlled materials and dynamic molecular systems that are in continuous communication (molecular exchange) with the external environment. Designing artificial materials that self-assemble and disassemble via conversion/consumption of a chemical fuel is a grand challenge in supramolecular chemistry, which requires a profound knowledge of the factors governing these complex systems. Here we focus on recently reported metal-coordinated monomers that polymerise in the presence of ATP and depolymerise upon ATP hydrolysis, exploring their fuel-regulated self-assembly/disassembly via multiscale molecular modelling. We use all-atom simulations to assess the role of ATP in stabilising these monomers in assemblies, and we then build on a minimalistic model to investigate their fuel-driven polymerization and depolymerization on a higher scale. In this way, we elucidate general aspects of fuel-regulated s...
ChemInform, 2014
The morphologies and functionalities of supramolecular architectures are governed entirely by the molecular design and the self-assembling field. Herein, we demonstrate that use of a microflow system to precisely regulate the selfassembling field enables control over the pathway for self-assembly of a designed molecule. By changing the flow rate, we could selectively create supramolecular nanofibers having various length and stabilities under nonequilibrium conditions.
Chemical Communication, 2018
Peptide 1 with an Ab42 amyloid nucleating core demonstrates step-wise self-assembly in water. Variation of temperature or solvent composition arrests the self-assembly to give metastable nano-particles, which undergo self-assembly on gradual increase in temperature and eventually produce kinetically controlled nanofibers and thermodynamically stable twisted helical bundles. Mechanical agitation of the fibers provided access to short seeds with narrow polydispersity index, which by mediation of seeded supramolecular polymerization establishes perfect control over the length of the nanofibers. Such pathway dependence and the length control of the supramolecular peptide nanofibers is exploited to tune the mechanical strength of the resulting hydrogel materials. Nature is a perfect engineer to design materials having complex structure and function through the mediation of noncovalent interaction. Over recent decades, scientists have ramped up efforts to mimic nature in designing supramolecular materials with such structure-functional control using bottom-up self-assembly. 1 However, unlike natural systems guided by out-of-equilibrium self-assembly, most of the supramolecular polymers are dictated by thermodynamically controlled single state and concentration-dependent self-assembly pathways. 2 Manner et al. were first to report living epitaxial crystallization mediated self-assembly in block co-polymeric micelles. 3 However, the recent understanding of pathway complexity, with the coexistence of multiple competitive pathways in a self-assembly process, provided a new paradigm and tool to control the fate of supra-molecular systems under a variety of conditions. 4 Arresting the monomer in the metastable state allows access to kinetically trapped species, 5 which can be employed in seeded supra-molecular polymerization to control the self-assembly with structural and dimensional precision, akin to the controlled living polymerization in covalent polymers. 6 Recently, the groups of Sugiyasu, Takeuchi and Würthner demonstrated elegant examples of pathway complexity in functionalized porphyrin and perylene bisimide to form kinetically or thermodynamically controlled aggregates by tweaking the conditions, e.g. temperature and solvents. 7 In another interesting example, Aida et al. demonstrated the competition of intra-vs. intermolecular hydrogen bonding to control the opening of metastable cage to 1-D self-assembly in corannulene molecules with multiple amide functionalities. 8 Interplay of dynamic covalent chemistry and self-replication was used by Otto et al. to grow kinetically controlled fibers in aqueous milieu from metastable macrocycles with excellent length control. 9 The nucleation-elongation model in amyloid fibril formation, as observed in prion infection, 10 provides a vital cue to study the pathway complexity to get insight into the fibrillation. 11 We postulate that self-assembly of short peptide fragments inspired from an amyloid nucleating core may act as a model system to study kinetically controlled living supramolecular polymerization and formation of hierarchical structures in water. Herein, we report formation of metastable nanoparticles, which eventually produce kinetically controlled nanofibers and thermodynamically stable twisted helical bundles. Adding short nanofiber seeds to the metastable nanoparticles allows access to kinetic nanofibers with excellent length control. These fibers are physically cross-linked to render hydrogels. Herein, we demonstrate tunable mechanical strength of the hydrogels as a result of pathway dependence and seed mediated length distribution of the peptide fibers. The peptide amphiphile 1 was designed by tethering a hydrophobic fluorenylmethyloxycarbonyl (Fmoc) group at the N-terminal and two hydrophilic lysine units at the C-terminal of a short peptide sequence N VFFA C (Scheme 1). The Fmoc-VFFA and the protonated lysine moieties maintain hydrophobic-hydrophilic balance to make 1 self-assemble in water (pH = 6). The attractive hydrogen bonding among the amide functionalities and p-p stacking interactions among the aromatic moieties promote parallel stacking of the amphiphiles to form secondary structures. To erase any pre-assembly history, 1 was isolated from dimethyl formamide (DMF), where it is molecularly dissolved. Temperature-dependent self-assembly of 1 in water was
Supramolecular Assembly of Peptide Amphiphiles
Accounts of Chemical Research, 2017
CONSPECTUS: Peptide 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 PAs, often become kinetically trapped in local minima along their self-assembly reaction coordinate, not unlike the pathways associated with protein folding. Furthermore, the assembly pathway can influence the shape, internal structure, and dimension of nanostructures and thereby affect their bioactivity. We discuss methods to map the energy landscape of a PA structure as a function of thermal energy and ionic strength and vary these parameters to convert between kinetically trapped and thermodynamically favorable states. We also demonstrate that the pathway-dependent morphology of the PA assembly can determine biological cell adhesion and survival rates. The dynamics associated with the nanostructures are also critical to their function, and techniques are now available to probe the internal dynamics of these nanostructures. For example, by conjugating radical electron spin labels to PAs, electron paramagnetic resonance spectroscopy can be used to study the rotational diffusion rates within the fiber, showing a liquidlike to solidlike transition through the cross section of the nanofiber. PAs can also be labeled with fluorescent dyes, allowing the use of super-resolution microscopy techniques to study the molecular exchange dynamics between PA fibers. For a weak hydrogen-bonding PA, individual PA molecules or clusters exchange between fibers in time scales as short as minutes. The amount of hydrogen bonding within PAs that dictates the dynamics also plays an important role in biological function. In one case, weak hydrogen bonding within a PA resulted in cell death through disruption of lipid membranes, while in another example reduced hydrogen bonding enhanced growth factor signaling by increasing lipid raft mobility. PAs are a promising platform for designing advanced hybrid materials. We discuss a covalent polymer with a rigid aromatic imine backbone and alkylated peptide side chains that simultaneously polymerizes and interacts with a supramolecular PA structure with identical chemistry to that of the side chains. The covalent polymerization can be "catalyzed" by noncovalent polymerization of supramolecular monomers, taking advantage of the dynamic nature of supramolecular assemblies. These novel hybrid structures have potential in selfrepairing materials and as reusable scaffolds for delivery of drugs or other chemicals. Finally, we highlight recent biomedical applications of PAs and related structures, ranging from bone regeneration to decreasing blood loss during internal bleeding.
Host–Guest Driven Self‐Assembly of Linear and Star Supramolecular Polymers
2008
MHz) spectrometer. All chemical shifts (δ) were reported in ppm relative to the proton resonances resulting from incomplete deuteration of the NMR solvents. 31 P NMR spectra were obtained using a Bruker AMX-400 (162 MHz) spectrometer. All chemical shifts (δ) were recorded in ppm relative to external 85% H 3 PO 4 at 0.00 ppm. Electrospray ionization ESI-MS experiments were performed on a ArH); 4.39 (t, 4H, ArCH, J = 7.7 Hz); 3.58 (t, 2H, CH 2 CH 2 OH, J = 6.3 Hz); 2.36-2.23 (m, 8H, ArCHCH 2); 2.04 (s, 12 H, ArCH 3); 1.49 (m, 2H, CH 2 CH 2 CH 2 OH); 1.28 (m, 6H, CH 2 CH 2 CH 3); 0.93 (t, 9H, CH 2 CH 2 CH 3 , J = 7.3 Hz). ESI-MS: m/z calcd for C 44 H 56 O 9 (729.4 Da) [M-H]-: 728.4; found 728.
Regulation of enzyme activity is key to the adaptation of cellular processes such as signal transduction and metabolism in response to varying external conditions. Synthetic molecular glues have provided effective systems for enzyme inhibition and regulation of protein-protein interactions. So far, all the molecular glue systems based on covalent interactions operated in equilibrium conditions. To emulate dynamic far-from-equilibrium biological processes, we introduce herein a transient supramolecular glue with controllable lifetime. The transient system uses multivalent supramolecular interactions between guanidium group-bearing surfactants and adenosine triphosphates (ATP), resulting in bilayer vesicle structures. Unlike the conventional fuels for non-equilibrium assemblies, ATP here plays the dual role of providing a structural component for the assembly as well as presenting active functional groups to “glue” enzymes on the surface. While gluing of the enzymes on the vesicles ac...
Localized Supramolecular Peptide Self-Assembly Directed by Enzyme-Induced Proton Gradients
Angewandte Chemie International Edition, 2017
Electrodes are ideal substrates for surface localized self-assembly processes.S patiotemporal control over such processes is generally directed through the release of ions generated by redox reactions occurring specifically at the electrode.The so-used gradients of ions proved their effectiveness over the last decade but are in essence limited to materialbased electrodes,c onsiderably reducing the scope of applications.H erein is described as trategy to enzymatically generate proton gradients from non-conductive surfaces.Inthe presence of oxygen, immobilization of glucose oxidase (GOx) on amultilayer film provides aflowofprotons through enzymatic oxidation of glucose by GOx. The confined acidic environment located at the solid-liquid interface allows the self-assembly of Fmoc-AA-OH (Fmoc = fluorenylmethyloxycarbonyl and A = alanine) dipeptides into b-sheet nanofibers exclusively from and near the surface.I nt he absence of oxygen, am ultilayer nanoreactor containing GOx and horseradish peroxidase (HRP) similarly induces Fmoc-AA-OH self-assembly.