Materials Discovery through Exploration of Biomolecular Space
Living systems provide the most sophisticated materials known. These materials and systems are created from a fully conserved set of just a few dozen building blocks common to all life forms. This observation begs a profound question: why can’t everything, including things that life has not explored, be made from biological building blocks? The Ulijn lab is taking steps to making this vision a reality, not by copying biology, but by developing methodology for bottom-up design, discovery and evolution of functional materials and biofluids to redesign biomolecules for a variety of applications.1 Some ongoing research projects: (i) Design of peptide modalities that give rise to formation of liquid condensates,2, 3 (ii) Mechano-responsive peptide crystals;4 (iii) Drug-matched peptide nanoparticles; (iv) Experimental learning and memory using sequence-adaptive peptide mixtures.5,6 Overall, our research demonstrates that peptides, and dynamically exchanging mixtures of peptides, show significant potential as designable and tunable nanomaterials for a variety of applications in biomedicine and green nanotechnology.
References: 1. Sheehan, et al., Chem. Rev., 2021, 121, 13869-13914.; 2. A. Jain, et al., J. Am. Chem. Soc., 2022, 144, 15002-15007.; 3. D. Sementa, et al., Angew. Chem. Int. Ed., 2023, e202311.; 4. R. Piotrowska, et al., Nature Materials, 2021, 20, 403-409.; 5. A. Jain, et al., Chem, 2022, 8, P1894-1905.; 6. S. Kassem, et al. J. Am. Chem. Soc., 2023, 145, 9800-9807.Research Topics
Learning and memory in designed peptide-systemsLearning and memory in designed peptide-systems
Systems chemistry aims to unravel how collective interactions of molecules give rise to emergent properties. We use the 20 gene-encoded amino acids to access complex, information rich and tractable systems. Our approach utilizes dynamic covalent peptide mixtures to design adaptive systems that store new information and create function as molecular fingerprints depending on the environmental conditions. Our dynamic peptide systems provide a much simpler parallel to biological systems and offer new avenues as discovery tools for adaptive liquids and condensed matter that are potentially more powerful compared with traditional combinatorial approaches, as selection occurs in direct competition instead of side by side.
Representative Works: 1. Jain, A.; McPhee, S. A.; Wang, T.; Nair, M. N.; Kroiss, D.; Jia, T. Z.; Ulijn, R. V. Tractable Molecular Adaptation Patterns in a Designed Complex Peptide System. Chem 2022, 8 (7), 1894–1905.;
2. Kassem, S.; McPhee, S. A.; Berisha, N.; Ulijn, R. V. Emergence of Cooperative Glucose-Binding Networks in Adaptive Peptide Systems. J. Am. Chem. Soc. 2023, 145 (17), 9800–9807.;
3. Pappas, C. G.; Shafi, R.; Sasselli, I. R.; Siccardi, H.; Wang, T.; Narang, V.; Abzalimov, R.; Wijerathne, N.; Ulijn, R. V. Dynamic Peptide Libraries for the Discovery of Supramolecular Nanomaterials. Nat. Nanotechnol. 2016, 11 (11), 960–967.
Responsive and adaptive porous peptide materials
Some materials can undergo reversible structural changes in response to changes in their environment, including relative humidity, e.g. due to evaporation. These water-responsive materials directly convert evaporation energy into mechanical energy and hold great potential as actuators for soft robotics, self-powered devices, and electromagnetic generators. We use short peptides as building blocks to uncover design principles that enhance chemo-mechanical responsiveness. Our design draws inspiration from biological systems, leveraging reconfigurable protein side chains, and employs crystal engineering principles to produce cost-effective, biocompatible, and environmentally friendly actuators.
Representative Works: 1. Piotrowska, R.; Hesketh, T.; Wang, H.; Martin, A. R. G.; Bowering, D.; Zhang, C.; Hu, C. T.; McPhee, S. A.; Wang, T.; Park, Y.; Singla, P.; McGlone, T.; Florence, A.; Tuttle, T.; Ulijn, R. V.; Chen, X. Mechanistic Insights of Evaporation-Induced Actuation in Supramolecular Crystals. Nat. Mater. 2021, 20 (3), 403–409.;
2.Sheehan, F. K.; Wang, H.; Podbevšek, D.; Naranjo, E.; Rivera-Cancel, J.; Moran, C.; Ulijn, R. V.; Chen, X. Aromatic Zipper Topology Dictates Water‐Responsive Actuation in Phenylalanine‐Based Crystals. Small 2023, 19 (27), 2207773.
Biomolecular liquids and dispersions
Condensate-based peptide systems promise opportunities to compartmentalize or segregate reactions and to gain precise (spatial and temporal) regulatory control over biomolecular processes in cells and test tubes. Our aim is to figure out the design rules to create liquid peptide materials with , including (i) controlled sequestering of fibers and molecules inside coacervates, resulting in unique architectures of liquid droplets with solid fiber networks, (ii) design and experimental and computational characterization of a series of new peptide modalities for liquid-liquid phase separation, which also reveal new fundamental insights into the role of backbone structuring; (iii) discovery of unique two- stage liquid-liquid-solid phase separation to achieve effective encapsulation upon drying.
Representative Works: 1.Jain, A.; Kassem, S.; Fisher, R. S.; Wang, B.; Li, T.; Wang, T.; He, Y.; Elbaum-Garfinkle, S.; Ulijn, R. V. J. Am. Chem. Soc. 2022, 144, 33, 15002–15007.;
2.Sementa, D; Dave, D.; Fisher, R.S.; Wang, T.; Elbaum-Garfinkle, S.; Ulijn, R.V. Sequence-Tunable Phase Behavior and Intrinsic Fluorescence in Dynamically Interacting Peptides. Angew. Chem. Int. Ed. 2023, 62, e2023114;
3.Dave, D. R.; Kassem, S.; Coste, M.; Tayarani-Najjaran, M.; Xu, L.; Zhang, S.; Podbevsek, D.; Macias, L. O.; Sementa, D.; Choudhury, M. A.; Veerasammy, K.; Doganata, S.; Weng, C.; Morales, J.; Wang, T.; Marianski, M.; Li, T.-D.; Chen, X.; Tu, R.; He, Y.; Ulijn, R. V. Adaptive and Space-Filling Peptide Self-Assembly Upon Drying. 2024.
Peptides for biomedical applications
By harnessing the rich chemistry of the natural amino acids, we design nanomaterials that can interact with biological systems. We focus on a variety of applications, including encapsulation and delivery of small molecule therapeutics and nucleic acids with peptide nanocarriers, design of enzyme responsive and biomimetic materials, scaffold production for tissue engineering, and development of sensors and imaging agents.
Representative Works: 1.Marciano, Y.; del Solar, V.; Nayeem, N.; Dave, D.; Son, J.; Contel, M.; Ulijn, R. V. Encapsulation of Gold-Based Anticancer Agents in Protease-Degradable Peptide Nanofilaments Enhances Their Potency. J. Am. Chem. Soc. 2023, 145 (1), 234–246.;
2.Huang, R. H.; Nayeem, N.; He, Y.; Morales, J.; Graham, D.; Klajn, R.; Contel, M.; O’Brien, S.; Ulijn, R. V. Self-Complementary Zwitterionic Peptides Direct Nanoparticle Assembly and Enable Enzymatic Selection of Endocytic Pathways. Adv. Mater. 2022, 34 (1), 2104962.;
3.Lampel, A.; McPhee, S. A.; Park, H. A.; Scott, G. G.; Humagain, S.; Hekstra, D. R.; Yoo, B.; Frederix, P. W. J. M.; Li, T. De; Abzalimov, R. R.; Greenbaum, S. G.; Tuttle, T.; Hu, C.; Bettinger, C. J.; Ulijn, R. V. Polymeric Peptide Pigments with Sequence-Encoded Properties. Science 2017, 356 (6342), 1064–1068.;
4.Kumar, M.; Ing, N. L.; Narang, V.; Wijerathne, N. K.; Hochbaum, A. I.; Ulijn, R. V. Amino-Acid-Encoded Biocatalytic Self-Assembly Enables the Formation of Transient Conducting Nanostructures. Nat. Chem. 2018, 10 (7), 696–703.
Automated directed discovery of peptide materials
Computational methods provide a powerful resource for mechanistic study and informed design of new peptides. We seamlessly integrate experimentation and computation such as molecular modeling, machine learning, and simulations to design and predict peptide behavior for new functional material design.
Representative Works: 1.Ramakrishnan, M.; van Teijlingen, A.; Tuttle, T.; Ulijn, R. V. Integrating Computation, Experiment, and Machine Learning in the Design of Peptide‐Based Supramolecular Materials and Systems. Angew. Chemie 2023, 135 (18), e202218067;
2.Frederix, P. W. J. M.; Scott, G. G.; Abul-Haija, Y. M.; Kalafatovic, D.; Pappas, C. G.; Javid, N.; Hunt, N. T.; Ulijn, R. V.; Tuttle, T. Exploring the Sequence Space for (Tri-)Peptide Self-Assembly to Design and Discover New Hydrogels. Nat. Chem. 2015, 7 (1), 30–37