Research in The Deming Group

Research in the Deming group is focused on synthesis, processing, characterization and evaluation of biological and biomimetic materials based on polypeptides. These materials are being studied since they can be prepared from renewable resouces, they can be biocompatible and biodegradable, and possess unique self-assembling properties. We utilize innovative chemistry techniques to synthesize materials with properties that rival the complexity found in biological systems. The polymers are then processed into ordered assemblies, which are characterized for both nanoscale structure as well as biological function. This interdisciplinary approach stimulates innovations and ideas which direct this research into new, exciting areas. Some current research projects are summarized below.

Applications for admission to our Graduate program are handled directly by the Bioengineering Department at http://www.bioeng.ucla.edu/or contact our graduate advisor

1) Transition Metal Catalysis in Polypeptide Synthesis

The goal of this research has been to use transition metal chemistry to produce synthetic block copolypeptide materials with precise control over comonomer sequence and composition and polymer molecular weight. The lack of well-defined synthetic polypeptides has limited their use in materials applications. We believe that the ability to prepare well-defined block copolypeptides will tremendously increase their potential as biomolecular materials. We have successfully developed organonickel initiators for the controlled, living polymerization of alpha-aminoacid-N-carboxyanhydrides (NCAs) into complex polypeptide sequences and architectures.

The mechanistic details of this polymerization system have been studied in detail and have led to the development of initiator systems based on other metals such as cobalt and iron. We continue to study the organometallic chemistry of this system in order to develop new initiators that will allow even greater control over polypeptide formation. The development of chiral, enantioselective initiators and chain-end functionalization chemistry are examples of accomplishments in this area. We also have recently pursued the formation of block copoly(beta-peptides) from beta-lactams using transition metal inititors. Recent work is focused on stereochemical control of NCA polymerizations and the metal-mediated synthesis of branched copolypeptides.

2) Polypeptide Hydrogels for Biomedical Applications

Protein-based hydrogels are used for many applications, ranging from food and cosmetic thickeners to support matrices for drug delivery and tissue replacement. These materials are usually prepared using proteins extracted from natural sources, which can give rise to inconsistent properties detrimental for medical applications. We have recently synthesized diblock copolypeptide amphiphiles containing charged and hydrophobic segments. Rather than forming micelles, dilute solutions of these copolypeptides surprisingly were found to form hydrogels with useful and unique properties, including high temperature stability and rapid healing after stress. The use of synthetic materials allows adjustment of copolymer chain length and composition, which we can vary to study their effect on hydrogel formation and properties. In addition to the amphiphilic nature of the polypeptides, their chain conformations, either a-helix, b-strand or random coil, were found to play key roles in gelation. This shape-specific supramolecular assembly was found to be integral to the gelation process, and provides new peptide-based hydrogels with potential for applications in biotechnology. We are currently exploring the assembly mechanisms in these materials, and also exploring the properties of the materials for a number of applications, including axon regernation. Collaborators: Prof. Michael Sofroniew(UCLA), Prof. Darrin Pochan (U. Delaware)

Lysine-Leucine diblock copolymer hydrogel (3.0 wt% in water)

Left: Cryo-TEM image (bar = 0.5 mm)

Right: schematic showing self-assembly

3) Self-Assembly of Block Copolypeptides in Aqueous Solution

We are examining the self-assembly of copolypeptides containing different combinations of uncharged hydrophilic, charged, and hydrophobic domains in aqueous environments. Beyond the usual types of aggregated structures (e.g. micelles, vesicles, and lamellar phases), we hope to identify new structures that result from the secondary structures found in the polypeptide domains. By varying the placement of these discrete domains along a polymer chain, we plan to prepare new structures for biomedical applications (including drug/gene delivery, artificial membranes, and bioactive surface coatings). Collaborators: Prof. Dan Kamei(UCLA), Prof. Lily Wu(UCLA), Prof. Tom Mason(UCLA), Prof. Darrin Pochan (U. Delaware)

(ethylene glycol-Lysine)-Leucine (K^P_mL_n) block copolypeptide vesicles in aqueous suspension

Left: K^P₆₀L₂₀, Middle: K^P₁₀₀L₂₀, Right: K^P₁₅₀L₄₀

4) Structural Materials from Self-Assembled Multi-Block Copolypeptides

Studies on our polypeptides in the solid-state are also underway. We plan to utilize the microphase separation characteristics of these block copolymers to form ordered materials useful as fibers, elastomers and environmentally responsive materials for biomedical applications (e.g. artificial tissues, sutures). The secondary structures found in polypeptides (rod-like helices and crystalline beta-sheets) will provide an additional component to phase separation in determining their internal structure. We also will take advantage of our catalysis chemistry that allows the preparation of multiple blocks (> 4) in the copolymer sequence. These features, not found in conventional block copolymers, should assist formation of new, hierarchically assembled structures with unconventional, but tunable, physical properties. Collaborators: Prof. Darrin Pochan (U. Delaware)

For more information e-mail us at demingt@seas.ucla.edu