Multifunctional Materials through Modular Protein Engineering

Department of Bioengineering, Stanford University, CA 94305, USA.
Advanced Materials (Impact Factor: 17.49). 08/2012; 24(29):3923-40. DOI: 10.1002/adma.201200051
Source: PubMed


The diversity of potential applications for protein-engineered materials has undergone profound recent expansion through a rapid increase in the library of domains that have been utilized in these materials. Historically, protein-engineered biomaterials have been generated from a handful of peptides that were selected and exploited for their naturally evolved functionalities. In recent years, the scope of the field has drastically expanded to include peptide domains that were designed through computational modeling, identified through high-throughput screening, or repurposed from wild type domains to perform functions distinct from their primary native applications. The strategy of exploiting a diverse library of peptide domains to design modular block copolymers enables the synthesis of multifunctional protein-engineered materials with a range of customizable properties and activities. As the diversity of peptide domains utilized in modular protein engineering continues to expand, a tremendous and ever-growing combinatorial expanse of material functionalities will result.

24 Reads
  • Source
    • "Moreover, proteins usually serve as cross-linkers via covalent (Michael addition [15], [16], enzyme reaction [17] or site selective conjugation [18], [19]) or non-covalent interactions (specific protein-peptide [20], protein-protein [21], [22] or protein-polysaccharide interactions [23]) in protein-based hydrogels, which require them to have multiple binding sites to their ligands. Some specific amino acid side chain groups such as the lysine’s ε-amine and cysteine’s sulphydryl endow favourable targets for cross-linking reactions [24], [25]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hydrogels have strong application prospects for drug delivery, tissue engineering and cell therapy because of their excellent biocompatibility and abundant availability as scaffolds for drugs and cells. In this study, we created hybrid hydrogels based on a genetically modified tax interactive protein-1 (TIP1) by introducing two or four cysteine residues in the primary structure of TIP1. The introduced cysteine residues were crosslinked with a four-armed poly (ethylene glycol) having their arm ends capped with maleimide residues (4-armed-PEG-Mal) to form hydrogels. In one form of the genetically modification, we incorporated a peptide sequence 'GRGDSP' to introduce bioactivity to the protein, and the resultant hydrogel could provide an excellent environment for a three dimensional cell culture of AD293 cells. The AD293 cells continued to divide and displayed a polyhedron or spindle-shape during the 3-day culture period. Besides, AD293 cells could be easily separated from the cell-gel constructs for future large-scale culture after being cultured for 3 days and treating hydrogel with trypsinase. This work significantly expands the toolbox of recombinant proteins for hydrogel formation, and we believe that our hydrogel will be of considerable interest to those working in cell therapy and controlled drug delivery.
    Full-text · Article · Sep 2014 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Protein-based hydrogels are promising materials for tissue engineering and drug delivery due to the unique properties of proteins such as perfect polydispersity, exact control over monomer sequence, ability to fine-tune molecular-level biochemical interactions, etc. This tutorial review summarizes recent progress on the preparation of protein-based hydrogels and their applications. Typically, we introduce two strategies of covalent and non-covalent ones for the preparation of hydrogels. Hydrogels prepared by the covalent strategy are stable and can respond to the conformational change of proteins. They can be applied for cells encapsulation, screening of drug molecules and heavy metals, etc. Hydrogels formed by non-covalent interactions are injectable physical hydrogels. The simple mixing preparation strategy and fast gelation kinetics guarantee the homogeneous encapsulation of cells and therapeutic agents within them. Therefore, they have been widely applied for the delivery of bioactive components, regenerative medicine, etc. The challenges that remained in this field are also summarized in this paper. We envision that rationally designed protein-based hydrogels will have broad applications in many areas including controlled delivery, tissue engineering, drug screening, etc.
    Full-text · Article · Nov 2012 · Chemical Society Reviews
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cells respond to their environment in complex and sometimes poorly understood ways. Protein, peptide and synthetic peptidomimetic ligands may all be used to stimulate cells via receptor signaling, using interactions that are often highly specific. Polymer substrates that present these ligands provide a promising way to control cell development, both for applications in biotechnology and for fundamental studies of cell biology. Here we review a large range of techniques that have been employed to create and characterize ligand-functionalized substrates, with a particular focus on techniques that allow specific and consistent stimulation.
    No preview · Article · Jan 2013 · Progress in Polymer Science
Show more