The ability to engineer a solvent-exposed surface of self-assembling coiled coils allows one to achieve a higher-order hierarchical assembly such as nano- or microfibers. Currently, these materials are being developed for a range of biomedical applications, including drug delivery systems; however, ways to mechanistically optimize the coiled-coil structure for drug binding are yet to be explored. Our laboratory has previously leveraged the functional properties of the naturally occurring cartilage oligomeric matrix protein coiled coil (C), not only for its favorable motif but also for the presence of a hydrophobic pore to allow for small molecule binding. This includes the development of Q, a rationally designed pentameric coiled coil derived from C. Here, we present a small library of protein microfibers derived from the parent sequences of C and Q bearing various electrostatic potentials with the aim to investigate the influence of higher-order assembly and encapsulation of candidate small molecule, curcumin. The supramolecular fiber size appears to be well-controlled by sequence-imbued electrostatic surface potential, and protein stability upon curcumin binding is well correlated to relative structure loss, which can be predicted by in silico docking. 
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                            Engineered protein–iron oxide hybrid biomaterial for MRI-traceable drug encapsulation
                        
                    
    
            Labeled protein-based biomaterials have become popular for various biomedical applications such as tissue-engineered, therapeutic, and diagnostic scaffolds. Labeling of protein biomaterials, including with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, has enabled a wide variety of imaging and therapeutic techniques. These USPIO-based biomaterials are widely studied in magnetic resonance imaging (MRI), thermotherapy, and magnetically-driven drug delivery, which provide a method for direct and non-invasive monitoring of implants or drug delivery agents. Where most developments have been made using polymers or collagen hydrogels, shown here is the use of a rationally designed protein as the building block for a meso-scale fiber. While USPIOs have been chemically conjugated to antibodies, glycoproteins, and tissue-engineered scaffolds for targeting or improved biocompatibility and stability, these constructs have predominantly served as diagnostic agents and often involve harsh conditions for USPIO synthesis. Here, we present an engineered protein–iron oxide hybrid material comprised of an azide-functionalized coiled-coil protein with small molecule binding capacity conjugated via bioorthogonal azide–alkyne cycloaddition to an alkyne-bearing iron oxide templating peptide, CMms6, for USPIO biomineralization under mild conditions. The coiled-coil protein, dubbed Q, has been previously shown to form nanofibers and, upon small molecule binding, further assembles into mesofibers via encapsulation and aggregation. The resulting hybrid material is capable of doxorubicin encapsulation as well as sensitive -weighted MRI darkening for strong imaging capability that is uniquely derived from a coiled-coil protein. 
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                            - Award ID(s):
- 1728858
- PAR ID:
- 10374254
- Date Published:
- Journal Name:
- Molecular Systems Design & Engineering
- Volume:
- 7
- Issue:
- 8
- ISSN:
- 2058-9689
- Page Range / eLocation ID:
- 915 to 932
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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