Rational design of enzyme-containing materials
Abstract
Synthetic materials are still rather simplistic compared to their biological counterparts. Proteins draw upon a diverse library of chemistries. They fold into precise hierarchical structures. Lastly, they possess selective responses to specific stimuli. Proteins, however, are typically not amenable for use outside of their native biological environment. Recently, we demonstrated that statistical trends in protein surface chemistry could be exploited to develop rationally designed random heteropolymers (RHPs). RHPs participate in interactions that mimic the behavior of chaperone-active intrinsically disordered proteins (IDPs). Experimentally, RHPs behave like chaperones and have been verified to stabilize a wide range of proteins in otherwise denaturing solutions. This has led to enhanced protein processability and adaptability in a variety of applications. Although all results have been positive with several enzyme-based functional materials demonstrated, they raise significant challenges to our fundamental understanding in the hybrid biomaterials and the fundamental design rules to interface synthetic and biopolymers. For this renewal proposal, we organized a team with complimentary expertise, i.e. polymer science and biostatistics, and aim to address two questions: 1. The quantification of various processing parameters that govern the macroscopic activity of enzyme-containing materials. This is to harvest successes we have achieved up to this point and to pave the path toward functional materials that meet demands to fully realize the technological potential of protein-containing materials and to better serve the community. 2. Development of understanding in the origin of observed success in terms of RHP stabilizing proteins regardless of specific protein characteristics and inherent variations in the RHP. Specifically, we will focus on analyzing and synthetically controlling the statistical segmental heterogeneity in RHPs to correlate it with the RHP solution phase behavior and protein stabilization. As a new class of polymers, RHPs present numerous opportunities yet challenge our understanding of heterogeneous systems. The proposed fundamental investigation comes from a totally new angle, i.e. statistical heterogeneity that has not been explored previously. A synergistic effort between polymeric material and statistical sequence analysis will lead to new insights in RHP design rules to bridge the gap between the synthetic and natural building blocks. Technically, enzyme-containing materials opened many opportunities to address biological function incorporation into synthetic matter to duplicate what has been seen in nature.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jun 25, 2021
- Source ID
- W911NF2110128
Entities
People
- Ting Xu
Organizations
- Army Contracting Command
- United States Army
- University of California, Berkeley