4.8 Article

Introducing a combinatorial DNA-toolbox platform constituting defined protein-based biohybrid-materials

Journal

BIOMATERIALS
Volume 35, Issue 31, Pages 8767-8779

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.06.048

Keywords

Biohybrid-materials; ECM (extracellular matrix); Elastin-like-protein; Genetic engineering; Molecular tecton-libraries; Self-assembly

Funding

  1. Institute for Macromolecular Chemistry
  2. Freiburg Institute for Advanced Studies (FRIAS)
  3. Competence Network of Functional Nanostructures (KFN)
  4. Baden-Wurttemberg Stiftung
  5. Ministry of Science, Research and the Arts (MWK) Baden-Wurttemberg
  6. German Science Foundation (DFG) BIOSS Centre for Biological Signalling Studies [SPP1623, EXC 294]
  7. Rectorate of the University of Freiburg

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The access to defined protein-based material systems is a major challenge in bionanotechnology and regenerative medicine. Exact control over sequence composition and modification is an important requirement for the intentional design of structure and function. Herein structural- and matrix proteins provide a great potential, but their large repetitive sequences pose a major challenge in their assembly. Here we introduce an integrative one-vector-toolbox-platform (OVTP) approach which is fast, efficient and reliable. The OVTP allows for the assembly, multimerization, intentional arrangement and direct translation of defined molecular DNA-tecton libraries, in combination with the selective functionalization of the yielded protein-tecton libraries. The diversity of the generated tectons ranges from elastine-, resilin, silk- to epitope sequence elements. OVTP comprises the expandability of modular biohybrid-materials via the assembly of defined multi-block domain genes and genetically encoded unnatural amino acids (UAA) for site-selective chemical modification. Thus, allowing for the modular combination of the protein-tecton library components and their functional expansion with chemical libraries via UAA functional groups with bioorthogonal reactivity. OVTP enables access to multitudes of defined protein-based biohybrid-materials for self-assembled superstructures such as nanoreactors and nanobiomaterials, e.g. for approaches in biotechnology and individualized regenerative medicine. (C) 2014 Elsevier Ltd. All rights reserved.

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