Immune responses to coiled coil supramolecular biomaterials

Jai S. Rudra, Pulak K. Tripathi, David A. Hildeman, Jangwook P. Jung, Joel H. Collier

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Self-assembly has been increasingly utilized in recent years to create peptide-based biomaterials for 3D cell culture, tissue engineering, and regenerative medicine, but the molecular determinants of these materials' immunogenicity have remained largely unexplored. In this study, a set of molecules that self-assembled through coiled coil oligomerization was designed and synthesized, and immune responses against them were investigated in mice. Experimental groups spanned a range of oligomerization behaviors and included a peptide from the coiled coil region of mouse fibrin that did not form supramolecular structures, an engineered version of this peptide that formed coiled coil bundles, and a peptide-PEG-peptide triblock bioconjugate that formed coiled coil multimers and supramolecular aggregates. In mice, the native peptide and engineered peptide did not produce any detectable antibody response, and none of the materials elicited detectable peptide-specific T cell responses, as evidenced by the absence of IL-2 and interferon-gamma in cultures of peptide-challenged splenocytes or draining lymph node cells. However, specific antibody responses were elevated in mice injected with the multimerizing peptide-PEG-peptide. Minimal changes in secondary structure were observed between the engineered peptide and the triblock peptide-PEG-peptide, making it possible that the triblock's multimerization was responsible for this antibody response.

Original languageEnglish (US)
Pages (from-to)8475-8483
Number of pages9
JournalBiomaterials
Volume31
Issue number32
DOIs
StatePublished - Nov 2010

Bibliographical note

Funding Information:
This research was supported in part by the National Institutes of Health (NIDCR grant number R21DE017703 and NIBIB grant number 1R01EB009701 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We thank Allyson Sholl and Adora Lin for help with the immunology studies and Stephen Macha for assistance with mass spectrometry. The circular dichroism and analytical ultracentrifugation studies were performed at the University of Chicago Biophysics Core facility.

Keywords

  • Immunogenicity
  • Regenerative medicine
  • Self-assembly
  • Tissue engineering

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