ABSTRACT
The precise structural control is known for self-assembly into closed spherical structures (e.g., micelles), but similar control of open structures is much more challenging. Inspired by natural tobacco mosaic virus, we present the use of a rigid-rod template to control the size of a one-dimensional self-assembly. We believe that this strategy is novel for organic self-assembly and should provide a general approach to controlling size and dimension.
Subject(s)
Nanostructures/chemistry , Peptides/chemical synthesis , Polymers/chemical synthesis , Aluminum Silicates/chemistry , Hydrophobic and Hydrophilic Interactions , Microscopy, Atomic Force , Microscopy, Electron, Transmission , Models, Molecular , Molecular Structure , Particle Size , Peptides/chemistry , Polyethylene Glycols/chemistry , Polymers/chemistry , Protein Conformation , Protein Structure, Secondary , Surface PropertiesABSTRACT
The majority of clinically used contrast agents (CAs) for magnetic resonance imaging have low relaxivities and thus require high concentrations for signal enhancement. Research has turned to multivalent, macromolecular CAs to increase CA efficiency. However, previously developed macromolecular CAs do not provide high relaxivities, have limited biocompatibility, and/or do not have a structure that is readily modifiable to tailor to particular applications. We report a new family of multivalent, biomacromolecular, genetically engineered protein polymer-based CAs; the protein backbone contains evenly spaced lysines that are derivatized with gadolinium (Gd(III)) chelators. The protein's length and repeating amino acid sequence are genetically specified. We reproducibly obtained conjugates with an average of 8-9 Gd(III) chelators per protein. These multivalent CAs reproducibly provide a high relaxivity of 7.3 mM (-1) s (-1) per Gd(III) and 62.6 mM (-1) s (-1) per molecule. Furthermore, they can be incorporated into biomaterial hydrogels via chemical cross-linking of the remaining free lysines, and provide a dramatic contrast enhancement. Thus, these protein polymer CAs could be a useful tool for following the evolution of tissue engineering scaffolds.
Subject(s)
Contrast Media/chemistry , Contrast Media/metabolism , Magnetic Resonance Imaging/methods , Protein Engineering , Chelating Agents/chemistry , Contrast Media/pharmacology , Gold/chemistry , Molecular Sequence Data , Molecular Structure , Polymers/chemistry , Water/chemistryABSTRACT
Current interest in biomaterials for tissue engineering and drug delivery applications have spurred research into self-assembling peptide amphiphiles (PAs). Nanofiber networks formed from self-assembling PAs can be used as biomaterial scaffolds with the advantage of specificity by the incorporation of peptide-epitopes. Imaging the materials noninvasively will give information as to their fate in vivo. We report here the synthesis and in vitro MR images of self-assembling peptide amphiphile contrast agents (PACAs) that form nanofibers. At 400 MHz using a 0.1 mM Gd(III) conjugate of the PA we observed a T(1) three times that of a control gel. The PA derivative was doped into various epitope bearing PA solutions and upon gelling resulted in a homogeneous biomaterial as imaged by MRI.
Subject(s)
Biocompatible Materials/chemistry , Magnetic Resonance Imaging , Peptides/chemistry , Contrast Media , Epitopes , Gels , Surface-Active AgentsABSTRACT
Self-assembled peptide amphiphile nanofibers have been investigated for their potential use as in vivo scaffolds for tissue engineering and drug delivery applications. We report here the synthesis of magnetic resonance (MR) active peptide amphiphile molecules that self-assemble into spherical and fiber-like nanostructures, enhancing T(1) relaxation time. This new class of MR contrast agents can potentially be used to combine high-resolution three-dimensional MR fate mapping of tissue-engineered scaffolds with targeting of specific cellular receptors.
