Research in biological condensed phases has exploded over the past decade. A framework of understanding relating to how sequence dictates phase behavior in biological systems is now emerging. However, there are still gaps in understanding at molecular level that permit rational, design of peptide sequences that display sequence-controlled phase behaviors. In our new paper we used the information available from various biological and bioinspired systems described in the literature to design simple de novo repeat sequences that form dynamic interacting peptide networks. Our designs are composed of repeats of tripeptide spacers (GSG, SGS, GLG) interspersed by a pattern of adhesive amino acids (R/H and Y). We show, using a combination of computation and experiment, that spacer editing is sufficient to direct backbone structuring and phase behavior. Unexpectedly, the droplets showed intrinsic fluorescent behavior that was dictated by the peptide sequence.
In this paper we use a systems chemistry approach to harness weak combinatorial interactions and show spontaneous emergence of network cooperativity. We study systems that are composed of selected mixtures of dipeptides chosen based on glucose binding sites from the protein data bank. A peptidase is included that can catalyze peptide bond formation, exchange and breakdown. Binding to glucose shifts the thermodynamic equilibrium toward sequences that have favorable interactions with glucose through side-chain interactions. We were able to identify networks of up to 16 interacting tetrapeptides that stabilize glucose through hydrogen bonding and CH-π interactions and highlight the crucial role of residue cooperativity in enhancing weak binding interactions, and the influence of input selection and history on the system's composition. The paper showcases fundamental systems properties that cannot be discovered or replicated with reductionist approaches.
In this new research, Ankit and Salma designed a multi-component biomolecular condensate capable of stabilizing and confining amyloids in its liquid interior, while they do not form outside the droplets. This was achieved by using a unique amphiphilic design which is part amyloid and part polyelectrolyte co-assembling with other liquid phase separating, charge complementary, polyelectrolytes. The design makes sure that the amyloids are tethered and confined to the liquid interior. This is of significant consequence as a minimalistic design feature for functional, multicomponent condensates that much like cellular environments take advantage of their heterogeneity to direct metabolic processes.
In this new paper, Ankit studied the collective properties of peptide mixtures composed of 10s to 100s of interacting peptides that can adapt their compositions to their environment. He developed a synthetic approach and analysis method to begin uncovering how complex biomolecule mixtures interact and collectively adapt to changes in their environment.
His experiment began with mixing a number of selected dipeptides, based on their ability to aggregate and interact. In the presence of thermolysin, a non-specific amidase known for its ability to hydrolyze and ligate dipeptides, the dipeptides dynamically recombine and form peptides with complex interaction patterns. It was then possible for Jain to track the formation and breakdown of peptides of different sequence within the mixtures. He observed that their patterns of interaction were strongly dictated by environmental conditions.
Glycosylation is a common biological post-synthetic modification significant, yet under-explored implications for enhancing functionality in designed supramolecular materials. In this JACS publication, we use simple self-assembling tripeptides containing polar amino acids Ser and Thr as sites for glycosylation. Striking observations from the computational modeling of these systems show that the conformational landscape of these simple tripeptides, typically pre-organized by F-F self-stacking interactions, is dramatically increased by glycosylation. This is underpinned by the generation of a diverse supramolecular interactome consisting of contributions from weaker interactions such as CH-π.
We also find striking and counter-intuitive differences between the two-polar amino acids studied, with the more hydrophobic Thr residue causing an overall reduction in aggregation propensity due to disruption of F/F hydrophobic collapse driven self-assembly by CH-π interactions. The glycosylation leads to increase in overall hydration of these peptides which is reflected in the changes in material properties such reduced formation of amyloid-like structures and enhanced thermostability. Therefore, we believe this to be a first step in understanding the changes in molecular interactions upon glycosylation and their implications in the design of self-assembling glycopeptide-based materials.
Richard's latest paper demonstrates peptide-functionalized nanoparticles that can communicate with cancer cells and slow their development. The work - detailed in a newly published paper in Advanced Materials - is based charge-complementary zwitterionic peptides that give rise to remarkably robust self-assembly behavior in biological media.
The peptide design was incorporated into MMP-responsive peptides, so that nanoparticle self-assembly was activated when they encounter cancer cells. The cells take up the particle aggregates, and thereby instruct the cells to slow their growth. Because the nanoparticles communicate only with the cancer cells, healthy cells aren’t impacted.
Rein has been awarded a U.S. Department of Defense's Vannevar Bush Faculty Fellowship - the agency's most prestigious single-investigator award. The five-year fellowship will provide $3 million to support Ulijn's work to understand how complex mixtures of molecules acquire functionality, and to repurpose this understanding to create new nanotechnology that is inspired by living systems.
Read more about the award.
As with most things in life, "seeing is believing" is also true in soft nanomaterials. Visualization of nanostructures with electron microscopy is limited to dry or frozen samples, whereas, traditional fluorescence microscopy has lower optical resolution and often involves a complex dye labeling procedure. The latest work by Mohit, with contributions from Jiye, Richard and Deborah demonstrates a new and remarkably simple method to fluorescently label peptide nanostructures for their visualization in solution with super-resolution microscopy. We show that by simply mixing a small amount (0.1 mole%) of a commercially available dye (Alexa) with cationic self-assembling peptides gives rise to selective electrostatic association of the dyes with the peptide nanostructure surface, which enables imaging using Stimulated Emission Depletion (STED) based super-resolution microscopy. Importantly, the method gave new insights into the hierarchical organization of peptide nanostructures, and enabled visualization of a metabolic transformation as demonstrated by enzymatic degradation of peptide nanofibers which could be imaged in real-time in situ. The ease and general scope of the method developed and the high resolution (approx. 50 nm) will open doors for potential in vivo imaging for bio-medical applications.
We are interested in developing approaches to produce melanin-like materials with precisely controlled properties by using a bio-inspired approach, but radically simplified so that properties can be optimized specifically for technological applications, thus going beyond biologically available structures.
In this manuscript- by Eileen and Ayala in collaboration with the group of Nurit Ashkenasy at Ben Gurion University of the Negev, Israel, and Tell Tuttle and colleagues at the University of Strathclyde, UK, we demonstrate the use of a self-assembling tripeptide as a precursor for enzymatic formation of nanofibrous melanin-like structures with well-defined, and controllable electronic properties. We demonstrate two-fold conceptual novelty in (i) the ability to control oxidation but retain a well-defined fibrous morphology, that does not have a known equivalent in biology, and (ii) demonstrate unprecedented conductivity that is enhanced by enzymatic oxidation, and is demonstrated to be mediated by proton charge transfer.
Water evaporation is a remarkably powerful process, providing a clean source of energy to power mechanical machines and devices. In a newly published paper in Nature Materials, PhD student Roxy Piotrowska and collaborators within CUNY and at The University of Strathclyde demonstrate the development of shape-shifting crystals that directly convert evaporation energy into powerful motions.
These water-responsive materials are based on supramolecular tripeptide crystals that contain nanoscale pores where water tightly binds, and these pores are interspersed with a molecular network of stiff and flexible regions that powerfully contract when humidity reaches a critical value. This results in the crystals temporarily losing their ordered patterns, until humidity is restored and the crystals regain their original shape. This newly designed process can be repeated over and over, and gives rise to a remarkably efficient method of harvesting evaporation energy to perform mechanical work.
Mohit's latest paper in Nature Chemistry demonstrates the use of amino acids as chemical signals to enable the active editing of a self-assembling semiconducting structure, which results in temporal control over nanostructures and consequent transient electronic conductivity. The work will be of potential use in interfacing electronics with biological system.
Chunqiu's latest paper shows reversible regulation of catalytic activity of supramolecular peptide catalyst achieved by conformational transition from random coil to β-hairpin by changing the pH, which results in the reversible formation of an ordered array of 'active sites' composed of hydrophobic binding pockets and catalytic histidine residues with significant esterase activity. The work provides a step toward formation of self-regulating supramolecular assemblies.
Melanins-the pigments that give color to skin, hair and eyes-have numerous useful qualities, including providing protection from cancer-causing UV radiation and free radicals, but also electronic conductance, adhesiveness and the capacity to store energy. We have developed a new approach for producing materials that not only mimic the properties of melanin, but also provide unprecedented control over expressing specific properties of the biopolymer, as published in Science. Unlike other biopolymers, such as DNA and proteins, where a direct link exists between the polymers ordered structures and their properties, melanin is inherently disordered, so directly relating structure to function is not possible. We found that the key to achieving polymers with controlled disorder is to start from systems that have variable order built in, which could be achieved by using self-assembling tripeptides with varying sequence as substrates for oxidative, biocatalytic polymerization. The discovery could enable the development of cosmetic and biomedical products.