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- Aronsson, Christopher
(författare)
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Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biomaterials are materials that are specifically designed to be in contact with biological systems and have for a long time been used in medicine. Examples of biomaterials range from sophisticated prostheses used for replacing outworn body parts to ordinary contact lenses. Currently it is possible to create biomaterials that can e.g. specifically interact with cells or respond to certain stimuli. Peptides, the shorter version of proteins, are excellent molecules for fabrication of such biomaterials. By following and developing design rules it is possible to obtain peptides that can self-assemble into well-defined nanostructures and biomaterials.The aim of this thesis is to create ”smart” and tunable biomaterials by molecular self-assembly using dimerizing –helical polypeptides. Two different, but structurally related, polypeptide-systems have been used in this thesis. The EKIV-polypeptide system was developed in this thesis and consists of four 28-residue polypeptides that can be mixed-and-matched to self-assemble into four different coiled coil heterodimers. The dissociation constant of the different heterodimers range from μM to < nM. Due to the large difference in affinities, the polypeptides are prone to thermodynamic social self-sorting. The JR-polypeptide system, on the other hand, consists of several 42-residue de novo designed helix-loop-helix polypeptides that can dimerize into four-helix bundles. In this work, primarily the glutamic acid-rich polypeptide JR2E has been explored as a component in supramolecular materials. Dimerization was induced by exposing the polypeptide to either Zn2+, acidic conditions or the complementary polypeptide JR2K.By conjugating JR2E to hyaluronic acid and the EKIV-polypeptides to star-shaped poly(ethylene glycol), respectively, highly tunable hydrogels that can be self-assembled in a modular fashion have been created. In addition, self-assembly of spherical superstructures has been investigated and were obtained by linking two thiol-modified JR2E polypeptides via a disulfide bridge in the loop region. ŒThe thesis also demonstrates that the polypeptides and the polypeptide-hybrids can be used for encapsulation and release of molecules and nanoparticles. In addition, some of the hydrogels have been explored for 3D cell culture. By using supramolecular interactions combined with bio-orthogonal covalent crosslinking reactions, hydrogels were obtained that enabled facile encapsulation of cells that retained high viability.The results of the work presented in this thesis show that dimerizing α–helical polypeptides can be used to create modular biomaterials with properties that can be tuned by specific molecular interactions. The modularity and the tunable properties of these smart biomaterials are conceptually very interesting andmake them useful in many emerging biomedical applications, such as 3D cell culture, cell therapy, and drug delivery.
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| 2. |
- Dånmark, Staffan, et al.
(författare)
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Tailoring Supramolecular Peptide-Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting
- 2016
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Ingår i: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 17:6, s. 2260-2267
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Tidskriftsartikel (refereegranskat)abstract
- Physical hydrogels are extensively used in a wide range of biomedical applications. However, different applications require hydrogels with different mechanical and structural properties. Tailoring these properties demands exquisite control over the supramolecular peptides with different affinities for dimerization. Four different mechanical properties of hydrogels using de novo designed coiled coil interactions involved. Here we show that it is possible to control the nonorthogonal peptides, designed to fold into four different coiled coil heterodimers with dissociation constants spanning from mu M to pM, were conjugated to star-shaped 4-arm poly(ethylene glycol) (PEG). The different PEG-coiled coil conjugates self-assemble as a result of peptide heterodimerization. Different combinations of PEG peptide conjugates assemble into PEG peptide networks and hydrogels with distinctly different thermal stabilities, supramolecular, and rheological properties, reflecting the peptide dimer affinities. We also demonstrate that it is possible to rationally modulate the self-assembly process by means of thermodynamic self-sorting by sequential additions of nonpegylated peptides. The specific interactions involved in peptide dimerization thus provides means for programmable and reversible self-assembly of hydrogels with precise control over rheological properties, which can significantly facilitate optimization of their overall performance and adaption to different processing requirements and applications.
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| 3. |
- Wickham, Abeni, et al.
(författare)
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Electroactive biomimetic collagen-silver nanowire composite scaffolds
- 2016
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Ingår i: Nanoscale. - Cambridge : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 8:29, s. 14146-14155
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Tidskriftsartikel (refereegranskat)abstract
- Electroactive biomaterials are widely explored as bioelectrodes and as scaffolds for neural and cardiac regeneration. Most electrodes and conductive scaffolds for tissue regeneration are based on synthetic materials that have limited biocompatibility and often display large discrepancies in mechanical properties with the surrounding tissue causing problems during tissue integration and regeneration. This work shows the development of a biomimetic nanocomposite material prepared from self-assembled collagen fibrils and silver nanowires (AgNW). Despite consisting of mostly type I collagen fibrils, the homogeneously embedded AgNWs provide these materials with a charge storage capacity of about 2.3 mC cm(-2) and a charge injection capacity of 0.3 mC cm(-2), which is on par with bioelectrodes used in the clinic. The mechanical properties of the materials are similar to soft tissues with a dynamic elastic modulus within the lower kPa range. The nanocomposites also support proliferation of embryonic cardiomyocytes while inhibiting the growth of both Gram-negative Escherichia coli and Gram-positive Staphylococcus epidermidis. The developed collagen/AgNW composites thus represent a highly attractive bioelectrode and scaffold material for a wide range of biomedical applications.
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