The objective of this proposal is to synthesize novel biomaterials with advanced mechanical properties using protein domains as building blocks. Natural materials, such as the muscle protein titin, have generated great interest due to their extraordinary strength, toughness and elasticity, currently unmatched in synthetic materials.
The specific aim of my research is to address this challenge by designing biopolymers possessing precise higher-ordered complexity inherent in proteins for combined strength and toughness. Such materials have potential applications in biomedical research as biodegradable tissue engineering scaffolds, surgical sutures, implants and prosthetics, as well as in drug delivery, among others. Our method involves an interdisciplinary approach that merges molecular dynamics, chemical biology and materials science. First, proteins identified through a detailed bioinformatics search of the protein databank will be analyzed by steered molecular dynamics (SMD) to determine their potential as mechanically resistant modular domains. SMD simulations provide a means of measuring the relative mechanical stability of a protein under an applied force, analogous to atomic force spectroscopy single-molecule experiments, prior to actual protein synthesis. Second, upon identification of potential protein candidates, genetic engineering and protein engineering techniques, coupled with chemical functionalization, will be used to obtain linear biopolymers with precisely controlled polymer chain length, composition, sequence, and stereochemistry. Using bacterial expression systems to synthesize the biopolymers offers a unique advantage over chemical synthesis in the ability to control these properties, making it feasible to readily fine tune the materials for select applications. Finally, single-molecule force spectroscopy (SMFS) experiments and nano-materials studies will be carried out to probe the effect of forces applied to the macromolecules and to further study their structure-property relationships. SMFS has become an invaluable tool in the field of biophysics and supramolecular chemistry, yielding vital information on the secondary interactions of the macromolecules at the single-molecule level, and revealing potential mechanisms of unfolding under an applied force. Public Abstract: Our research project aims to address the challenge of preparing novel biomaterials that mimic the body's natural mechanical proteins for use in biomedical research. Using proteins as building blocks ensures that our polymers will be biocompatible and biodegradable, unlike synthetic biomaterials which require additional modification. Another advantage of protein-based materials is the versatility derived from selectively incorporating domains with desired properties for use in specific biological applications. ? ? ?
| 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 |
| Aguilar, Manuel B; Lopez-Vera, Estuardo; Heimer de la Cotera, Edgar P et al. (2007) I-conotoxins in vermivorous species of the West Atlantic: peptide sr11a from Conus spurius. Peptides 28:18-23 |
