Bottom-Up Peptide Design

Matthew (Lake) Kubilius

Condensation polymerization reactions, including those of liquid-phase peptide synthesis, generally yield polymers with a polydispersity index (PDI) of around 2. Though higher PDI's are seen for other polymerization mechanisms, this non-narrow range of chain lengths gives rise to irregularities in their self-assembled structures. For optimal self-assembly, peptides coming together should have a PDI very close to 1. To achieve such a low PDI in a condensation reaction, some new, additional rate control mechanism must be introduced. Synthesizing peptides with alternating hydrophobic and hydrophilic amino acids results in a polymer with increasing amphipathic character as chain length increases. Thus, it should be possible to minimize the PDI of such systems by presenting the bulk reaction phase with an interface that preferentially sequesters longer polymers. Proving and characterizing this mechanism is of special interest both for its implications to polymerization processes and interfacial peptide self-assembly.

Lorraine Leon

Rationally designed peptide molecules can be used to template inorganic nanostructures. The inspiration for this work comes from nature, where biological molecules form interfaces that assemble patterns of chemical functionality with exceptional precision. The role of dynamics during the assembly of biological molecules appears to be important for mineralization processes. Applying model sheet-forming peptides at interfaces explores the dynamics of assembly as a template for mineral growth. The peptide molecules are rationally designed to have amphiphilic properties and a propensity for sheet-like secondary structure. These designed peptides are deposited at the air/water interface to explore the dynamics of their self-assembly and investigate their 2D order. To characterize the phase behavior, techniques such as Langmuir Blodgett and Brewster Angle Microscopy are used. In addition, verification of the hypothesized sheet-forming propensity is confirmed using both Circular Dichroism and Attenuated Total Reflection Fourier Transform Infrared Spectroscopy, while the characterization of the inorganic phase is done using Transmission Electron Microscopy, Electron Diffraction, and Atomic Force Microscopy.

Thermodynamic analysis of structure formation with increasing pressure allows an understanding of the nature of self-assembly with iterative changes in the peptide sequence. Additionally, it looks at the dynamics of the self-assembled state, where the organic phase switches between short- and long-range order as a function of surface pressure. This model system explores the influence of electrostatic interactions on self-assembly, and additionally, the influence of short- and long-range order on the nucleation and growth of inorganic material. This is in contrast to a system that starts with a well-ordered preformed template that defines the epitaxial growth of the mineral phase. Two versions of the model peptides are constructed by substituting histidine for glutamic acid in order to nucleate Au nanocrystals in both the short and long range ordered organic matrix, to show that the phase behavior of the peptide influences the crystallinity and shape of the templated nanocrystals.

Projects:

Bottom-Up Peptide Design

Protein Dynamics At the Air-Water Interface.html

Interfacial Crystallization

Polyelectrolyte (DNA)-condensation

Bio-Mineralization

Folding and Fishing

Drug Delivery

Biosensing

Polymer Electrolytes

Janus Particles At Interfaces