Multiplexed protein caging: orthogonal and on-command release of angiogenesis-promoting factors

Hochschulschrift

Zusammenfassung: Materials that are capable of changing their physical, chemical or biological properties in response to an external stimulus are called smart materials and have broadened the field of material science for a new spectrum of technical applications. Especially interesting for biomedical applications are biohybrid materials. Such materials are composed of a biological polymer and a synthetic polymeric backbone. Once incorporated into a synthetic matrix such biomolecules act as biological switches and translate small changes in the environmental conditions into macromolecular changes of the materials. The advantages of using biological polymers with inherent switch functions are fairly obvious. Owing their biological origin, they perform best under physiological conditions and are able to react to physiologically relevant changes of a large variety of signals including small molecules such as drugs or metabolites. As standardization of biological molecules with diverse functions has been a major goal of synthetic biology, a large variety of well characterized biological switches is available to find their application in material science. Here, the development of new biohybrid materials which respond to the physiologically compatible stimulus fluorescein is presented. Two different approaches for the realization of this goal were pursued. First, a biohybrid hydrogel which translates changes in fluorescein concentrations into a gel-to-sol transition, which could find possible applications in drug delivery, has been developed on the basis of the fluorescein-responsive anticalin FluA and the highly specific interaction of the hexahistidine peptide motif with immobilized nickel ions. In addition it was investigated if the native chemical reaction might be used for the development of a fluorescein-responsive hydrogel. In the second approach the concept of controlled caging and uncaging of biological compounds was utilized. A protein cage with is capable of caging Fc.- tagged growth factors to an agarose matrix via the adaptor protein FluA was developed. Thus, the protein cage translates changes in fluorescein concentration into changes of growth factor concentrations. Further, this fluorescein-responsive protein cage was combined with a novobiocin-responsive protein cage previously reported by Karlsson et al.[1] for the development of a tool for the multiplexed uncaging of growth factors. Considering that the vast majority of cellular processes are regulated by proteins such as growth factors and that de-regulated signaling is the basis for major and chronic diseases, this tool is of interest in both, fundamental and applied biological research and we believe that it will be a valuable asset in various biomedical settings

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Universität Freiburg, Dissertation, 2015

Classification and Topics

• Keyword: Arzneimittelentwicklung ; Arzneimitteldesign

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2015
• Creator: Hotz, Natascha
• Contributor: Weber, Wilfried

Further information

• DOI: 10.6094/UNIFR/10160
• URN: urn:nbn:de:bsz:25-freidok-101604
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 10:51 AM CEST