Spinning Peptides, Not Webs, From Spider Silk
Scientists design a novel protein-based watery gel that could help keep drugs where they are needed
Image reproduced by permission of Xiuzhi S. Sun and The Royal Society of Chemistry from Soft Matter, 2011, 7, 8905-8912, DOI: 10.1039/C1SM05157A.
Results: Combining proteins from spider silk and human muscle, scientists from Kansas State University, Pacific Northwest National Laboratory, and the University of Nebraska designed a small protein with big applications. The small protein or peptide, which forms water-soluble molecular chains called hydrogels, has potential medical applications including more effective drug delivery. The team tested the new peptide using swine flu vaccine and showed it was biologically safe and improved the vaccine's effectiveness by approximately 70 compared with a commercial oil-based pharmaceutical additive. This research was featured on a cover of Soft Matter, October 2011.
Why it matters: Keeping cancer-fighting agents and other drugs near their targets is important in order to kill the dangerous cells without harming the innocent bystanders. Hydrogels can help keep disease-fighting drugs or immune-enhancing vaccines corralled. For example, hydrogels could be used in liquid injection agents that become gelatinous in the human body to keep drugs around cancerous tumors and away from sensitive tissues nearby.
Methods: In this study, the scientists used two native functional sequences from spider flagelliform silk protein and a trans-membrane motif of human muscle L-type calcium channel to design the novel small protein, known as peptide, h9e. The protein is able to assemble itself, given the right conditions.
Once created, the h9e peptide formed two novel hydrogels in a calcium ion solution and acidic pH conditions—h9e Ca2+ hydrogel and h9e acidic hydrogel. The shear-thinning, rapid-strength-recovering h9e Ca2+ hydrogel proved to have potential for drug delivery and tissue-engineering applications and was tested on mice as an injectable adjuvant for H1N1 swine influenza virus killed vaccine. The study showed it was biologically safe, improved immune response on killed H1N1 virus antigen by approximately 70%, and induced a similar H1N1-specific IgG1 antibody response compared with an oil-based commercial adjuvant.
To understand the formation of these rationally designed peptide hydrogels, the researchers used electrospray ionization and then analyzed the resulting ions in a high-resolution mass spectrometer. The mass spectrometry experiments were conducted to identify possible precursors of the peptide assembly and nanofiber crossing and how the calcium became bound to the peptides.
What's next: Mass spectrometry will be used to better characterize the initial stages of self-assembly of these materials. Similar tools will also be used to obtain a better understanding of self-assembly and the properties of other materials such as catalytically active nanoparticles produced through solution-phase synthetic approaches.
Funding: Targeted Excellence Program and Center for Biobased Polymers by Design at Kansas State University, from the Kansas Agricultural Experiment Station.
User Facility: EMSL
Research Team: Hongzhou Huang, Jishu Shi, Ziyan Liu, and Xiuzhi S. Sun, Kansas State University; Julia Laskin, Pacific Northwest National Laboratory; and David S. McVeyd, University of Nebraska
Reference: Huang H, J Shi, J Laskin, Z Liu, DS McVey, and XS Sun. 2011. "Design of a shear-thinning recoverable peptide hydrogel from native sequences and application for influenza H1N1 vaccine adjuvant." Soft Matter 7(19):8905-8912. DOI: 10.1039/C1SM05157A (cover date: October 7, 2011).