Seminar Speaker: Nairiti Sinha, University of California, Santa Barbara

“Computationally-informed peptides as modular building blocks for supramolecular self-assembly”

Abstract

The utilization of biomacromolecules to engineer self-assembled materials that display target structure and function at the nanoscale is an active area of new materials research. Peptides that are short sequences of amino acids are excellent candidates for this purpose. Computational prediction of peptide sequences and in silico quantification of their secondary, tertiary, and quaternary structure has further enabled faster screening and deterministic design of peptide-based biomaterials. In the first part of my talk, I will discuss the utility of short, non-natural, computationally designed peptides that form artificial coiled coils called bundlemers as globular protein mimics and molecular Legos for supramolecular self-assembly. Via a feedback cycle between experiments and sequence-optimization algorithms, I have tested multiple peptide designs for successful bundlemer formation. I will present small angle neutron scattering (SANS) results that not only confirm that all bundlemers are robust nanocylinders but also shed light on their sequence-sensitive colloid-like solution behavior. Next, I will discuss a physical-chemical self-assembly method that was employed to polymerize the bundlemer units into flexible chain-like and rigid rod-like supramolecular polymers. The polymers were characterized using SANS and transmission electron microscopy (TEM). The difference in the bending dynamics of the polymers was further corroborated by neutron spin echo (NSE) spectroscopy measurements, which I will also present in my talk. Such bundlemer-based polymers can form tunable lyotropic liquid crystals and can also function as model systems to study similar protein assemblies in nature. In the second part of my talk, I will present my work involving the coacervation of oppositely charged polypeptides. The balance of electrostatic and hydrophobic forces is critical during protein folding events and misfolding can result in various diseases. My investigation reveals that this balance is crucial even in simple mixtures of poly-L-lysine and poly-L-glutamic acid that form new mixed phases such as partially coalescing droplets and dynamic networks of droplets. The presence of such complex morphologies coupled with molecular dynamics simulations results suggest that a subtle competition exists between non-equilibrium beta-sheet assembly and equilibrium coacervate formation; I will discuss these new results and their implications in my talk.

Speaker Biography

Dr. Nairiti Sinha completed her Ph.D. in Materials Science and Engineering at the University of Delaware in 2020. As a graduate student, she was also affiliated with NIST Center for Neutron Research (NCNR) at the National Institute of Standards and Technology (NIST), Gaithersburg, Maryland. As part of her doctoral thesis, Nairiti investigated the sequence design, solution behavior, dynamics and self-assembly of synthetic peptides called bundlemers. She received the ACS POLY/PMSE Excellence in Graduate Research Award in 2020 for her Ph.D. research and has delivered multiple invited talks on her Ph.D. work. She is currently a postdoctoral researcher at the Materials Research Laboratory at the University of California Santa Barbara where she is investigating molecular design-driven structure-property relationships in various materials such as coacervates, hydrogels and biological nanocomposites. Nairiti was selected for the Rising Stars in Soft and Biological Matter Symposium 2022 for her postdoctoral research that elucidates the balance of interactions in coacervating mixtures of homochiral peptides.