The proposed research investigates a biomimetic modular polymer design as a new strategy to achieve advanced biomaterials. The broad, long-term objective of this research is to develop rational design of biomaterials having high order structures for advanced properties. A specific challenge in biomaterials research is to design a polymer that has a combination of mechanical strength, fracture toughness, and elasticity - three fundamental mechanical properties that are highly desired but usually exclusive to each other in polymeric materials. Many structural biopolymers, such as the muscle protein titin, employ modular domain structures to achieve the combination of these three fundamental mechanical properties in one system. We propose to mimic the modular domain design in synthetic biomaterials. Specifically, we propose to synthesize and investigate biomimetic modular polymers having the following modules: (1) quadruple hydrogen bonding modules, (2) peptidomimetic beta-sheet modules, and (3) small protein modules. Our hypothesis is that the introduction of well-defined modular domain structures into synthetic biopolymers should lead to biomaterials having a combination of mechanical strength, toughness, and elasticity. Whereas numerous biomedical applications can be envisioned for this type of biomaterial, this proposal is focused on developing model polymers having modular domain structures with which to study the fundamental structure-property correlation in synthetic biomaterials. Through the proposed studies the following specific aims will be accomplished: (1) Synthesis and studies on discrete oligomers and polymers using well defined quadruple hydrogen bonding modules; (2) Synthesis and studies on discrete oligomers and polymers containing peptidomimetic a-sheet modules; (3) Synthesis and studies on discrete oligomers and polymers using protein G domain III (PG3) as module; and (4) Systematic investigation on the mechanical properties of the discrete oligomers as well as the high mass polymers made from the above modules at single-molecule, nanoscopic and macroscopic levels.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
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Medicinal Chemistry Study Section (MCHA)
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Moy, Peter
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University of California Irvine
Schools of Arts and Sciences
United States
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Kushner, Aaron M; Guan, Zhibin (2011) Modular design in natural and biomimetic soft materials. Angew Chem Int Ed Engl 50:9026-57
Guzman, Dora L; Randall, Arlo; Baldi, Pierre et al. (2010) Computational and single-molecule force studies of a macro domain protein reveal a key molecular determinant for mechanical stability. Proc Natl Acad Sci U S A 107:1989-94
Yu, Ting-Bin; Bai, Jane Z; Guan, Zhibin (2009) Cycloaddition-promoted self-assembly of a polymer into well-defined beta sheets and hierarchical nanofibrils. Angew Chem Int Ed Engl 48:1097-101
Kushner, Aaron M; Vossler, John D; Williams, Gregory A et al. (2009) A biomimetic modular polymer with tough and adaptive properties. J Am Chem Soc 131:8766-8
Guzman, Dora L; Roland, Jason T; Keer, Harindar et al. (2008) Using steered molecular dynamics simulations and single-molecule force spectroscopy to guide the rational design of biomimetic modular polymeric materials. Polymer (Guildf) 49:3892-3901
Kushner, Aaron M; Gabuchian, Vahe; Johnson, Evan G et al. (2007) Biomimetic design of reversibly unfolding cross-linker to enhance mechanical properties of 3D network polymers. J Am Chem Soc 129:14110-1
Oh, Keunchan; Guan, Zhibin (2006) A convergent synthesis of new beta-turn mimics by click chemistry. Chem Commun (Camb) :3069-71