Suchergebnisse

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. ; Funding Agencies|Swedish Research Council [621-2011-4319]; Swedish Foundation for Strategic Research [ICA10-0002]; Linkoping University; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009 00971]

We demonstrate a novel route for hierarchical self-assembly of sub-micrometer-sized peptide superstructures that respond to subtle changes in Zn2+ concentration. The self-assembly process is triggered by a specific folding-dependent coordination of Zn2+ by a de novo designed nonlinear helix-loop-helix peptide, resulting in a propagating fiber formation and formation of spherical superstructures. The superstructures further form larger assemblies that can be completely disassembled upon removal of Zn2+ or degradation of the nonlinear peptide. This flexible and reversible assembly strategy of the superstructures enables facile encapsulation of nanoparticles and drugs that can be released by means of different stimuli. ; Funding Agencies|Swedish Research Council [621-2011-4319]; Swedish Foundation for Strategic Research [ICA10-0002]; Linkoping University; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]

Tumor associated macrophages (TAM) are key pathogenic factors in neoplastic diseases. They are known to have plasticity and can polarize into two opposing phenotypes, including the tumoricidal M1 and the protumoral M2 phenotypes with high prevalence of M2-phentoypes in patients with poor prognosis. Strategies for targeting M2-TAM may consequently increase the efficacy of therapeutic strategies for cancer treatment. Gold nanorod-assisted plasmonic photothermal therapy (PPTT) has emerged as a promising treatment for cancer but the effects of macrophage polarization parameters in the performance of this new treatment modality is still unknown. Herein, human monocytic THP-1 cells were polarized into two opposite phenotypic macrophages (M1-TAM and M2-TAM) and their response to PPTT was examined. M2-TAM exhibits a three-fold increase in AuNP uptake compared to M1-TAM. Laser irradiation results in selective killing of pro-tumoral M2-TAM after treatment with AuNPs with limited effects on anti-tumoral M1-TAM. A positive correlation between the expression of CD206 marker and the AuNP uptake may indicate the role of CD206 in facilitating AuNP uptake. Our findings also suggest that the differences in AuNP avidity and uptake between the M1-TAM and M2-TAM phenotypes may be the rationale behind the effectiveness of PPTT in the treatment of solid tumors. ; Funding Agencies|Binational Fulbright Commission in Egypt [99869795N]; Swedish Research Council (VR)Swedish Research Council [2017-04475]; Swedish Foundation for Strategic Research (SFF)Swedish Foundation for Strategic Research [FFL15-0026]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [KAW 2016.0231]; Swedish Cancer Foundation [CAN 2017/430]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]

Coiled coils are characterized by an arrangement of two or more alpha-helices into a superhelix and one of few protein motifs where the sequence-to-structure relationship to a large extent have been decoded and understood. The abundance of both natural and de novo designed coil coils provides a rich molecular toolbox for self assembly of elaborate bespoke molecular architectures, nanostructures, and materials. Leveraging on the numerous possibilities to tune both affinities and preferences for polypeptide oligomerization, coiled coils offer unique possibilities to design modular and dynamic assemblies that can respond in a predictable manner to biomolecular interactions and subtle physicochemical cues. In this review, strategies to use coiled coils in design of novel therapeutics and advanced drug delivery systems are discussed. The applications of coiled coils for generating drug carriers and vaccines, and various aspects of using coiled coils for controlling and triggering drug release, and for improving drug targeting and drug uptake are described. The plethora of innovative coiled coil-based molecular systems provide new knowledge and techniques for improving efficacy of existing drugs and can facilitate development of novel therapeutic strategies. (c) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). 1. Introduction 27 2. The coiled coil motif 27 3. Coiled coils and coiled coil-hybrids for drug delivery and therapeutics 30 3.1. Coiled coils in liposome drug delivery systems 30 3.2. Lipidated coiled coils for assembly of virus-like particles 31 3.3. Coiled coil nanoparticles 31 3.4. Coiled coil nanocarriers 33 3.5. Coiled coil polymer-hybrids 33 3.6. Coiled coil-based hydrogels 36 3.7. Coiled coil inorganic nanoparticle hybrids 37 3.8. Coiled coils combined with cell penetrating peptides 37 3.9. Coiled coils for improved targeting 38 ; Funding Agencies|Swedish Foundation for Strategic Research (SFF)Swedish Foundation for Strategic Research [FFL15-0026, RMX18-0039]; Swedish Government Strategic Research Area inMaterials Science on Functional Materials at Linkoping University [2009-00971]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [KAW 2016.0231]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2017-04475]; Cancer Foundation [17 0534]

Matrix Metalloproteinase-7 (MMP-7) is a proteolytic enzyme overexpressed in different pathological conditions, including cancer, infection, and cardiovascular diseases, and is a relevant diagnostic biomarker and potential drug target. Here we demonstrate rapid and selective detection of MMP-7 with a limit-of-detection of 6 pg/mL and a dynamic range from 1 x 10(-2) to 1 x 10(3) ng/mL using a peptide decorated gold nanoparticle/carbon nanotube electrochemical sensor. The sensor could be operated in diluted human serum and synthetic urine, with high specificity towards MMP-7. Moreover, the integration of nanomaterials in the sensing electrode significantly increased the signal-to-background ratio and strongly improved the stability of the sensor when compared to a conventional gold electrode. The simple and cost-effective fabrication and the ease of use make this sensor a very promising protease detection device for diagnostics and drug development. ; Funding Agencies|Swedish Strategic Research FoundationSwedish Foundation for Strategic Research [SSF FFL15-0174, FFL15-0026]; Swedish Research CouncilSwedish Research Council [VR 2019-04690, VR 2017-04475]; Swedish Cancer Foundation [CAN 2017/430]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]; Wallenberg Academy Fellow Program [KAW 2015.0127, KAW 2016.0231]

Protein-metal ion interactions are ubiquitous in nature and can be utilized for controlling the self-assembly of complex supramolecular architectures and materials. Here, a tunable supramolecular hydrogel is described, obtained by self-assembly of a Zn2+-responsive peptide-hyaluronic acid hybrid synthesized using strain promoted click chemistry. Addition of Zn2+ triggers folding of the peptides into a helix-loop-helix motif and dimerization into four-helix bundles, resulting in hydrogelation. Removal of the Zn2+ by chelators results in rapid hydrogel disassembly. Degradation of the hydrogels can also be time-programed by encapsulation of a hydrolyzing enzyme within the gel, offering multiple possibilities for modulating materials properties and release of encapsulated species. The hydrogel further shows potential antioxidant properties when evaluated using an in vitro model for reactive oxygen species. ; Funding Agencies|Swedish Research Council (VR); Swedish Foundation for Strategic Research (SSF); Carl Trygger Foundation; Forum Scientium; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO Mat LiU) [2009 00971]

The development of chiral optoelectronic materials is of great interest due to their potential of being utilized in electronic devices, biosensors, and artificial enzymes. Herein, we report the chiral optical properties and architectural arrangement of optoelectronic materials generated from noncovalent self-assembly of a cationic synthetic peptide and five chemically defined anionic pentameric oligothiophenes. The peptide-oligothiophene hybrid materials exhibit a three-dimensional ordered helical structure and optical activity in the pi-pi* transition region that are observed due to a single chain induced chirality of the conjugated thiophene backbone upon interaction with the peptide. The latter property is highly dependent on electrostatic interactions between the peptide and the oligothiophene, verifying that a distinct spacing of the carboxyl groups along the thiophene backbone is a major chemical determinant for having a hybrid material with distinct optoelectronic properties. The necessity of the electrostatic interaction between specific carboxyl functionalities along the thiophene backbone and the lysine residues of the peptide, as well as the induced circular dichroism of the thiophene backbone, was also confirmed by theoretical calculations. We foresee that our findings will aid in designing optoelectronic materials with dynamic architectonical precisions as well as offer the possibility to create the next generation of materials for organic electronics and organic bioelectronics. ; Funding Agencies|Knut and Alice Wallenberg Foundation; Swedish Foundation for Strategic Research; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]

Conducting polymers are routinely used in optoelectronic biomaterials, but large polymer polydispersity and poor aqueous compatibility complicate integration with biomolecular templates and development of discrete and defined supramolecular complexes. Herein, we report on a chiro-optical hybrid material generated by the self-assembly of an anionic peptide and a chemically defined cationic pentameric thiophene in aqueous environment. The peptide acts as a stereochemical template for the thiophene and adopts an a-helical conformation upon association, inducing optical activity in the thiophene r-n * transition region. Theoretical calculations confirm the experimentally observed induced structural changes and indicate the importance of electrostatic interactions in the complex. The association process is also probed at the substrate-solvent interface using peptide-functionalized gold nanoparticles, indicating that the peptide can also act as a scaffold when immobilized, resulting in structurally well-defined supramolecular complexes. The hybrid complex could rapidly be assembled, and the kinetics of the formation could be monitored by utilizing the local surface plasmon resonance originating from the gold nanoparticles. We foresee that these findings will aid in designing novel hybrid materials and provide a possible route for the development of functional optoelectronic interfaces for both biomaterials and energy harvesting applications. ; Funding Agencies|Knut and Alice Wallenberg Foundation; Swedish Foundation for Strategic Research; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]

Hydrogels are used in a wide range of biomedical applications, including three-dimensional (3D) cell culture, cell therapy and bioprinting. To enable processing using advanced additive fabrication techniques and to mimic the dynamic nature of the extracellular matrix (ECM), the properties of the hydrogels must be possible to tailor and change over time with high precision. The design of hydrogels that are both structurally and functionally dynamic, while providing necessary mechanical support is challenging using conventional synthesis techniques. Here, we show a modular and 3D printable hydrogel system that combines a robust but tunable covalent bioorthogonal cross-linking strategy with specific peptide-folding mediated interactions for dynamic modulation of cross-linking and functionalization. The hyaluronan-based hydrogels were covalently cross-linked by strain-promoted alkyne-azide cycloaddition using multi-arm poly(ethylene glycol). In addition, ade novodesigned helix-loop-helix peptide was conjugated to the hyaluronan backbone to enable specific peptide-folding modulation of cross-linking density and kinetics, and hydrogel functionality. An array of complementary peptides with different functionalities was developed and used as a toolbox for supramolecular tuning of cell-hydrogel interactions and for controlling enzyme-mediated biomineralization processes. The modular peptide system enabled dynamic modifications of the properties of 3D printed structures, demonstrating a novel route for design of more sophisticated bioinks for four-dimensional bioprinting. ; Funding Agencies|Swedish Foundation for Strategic Research (SFF)Swedish Foundation for Strategic Research [FFL15-0026]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009-00971]; Carl Tryggers Foundation [CTS15:7, CTS18:5]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [KAW 2016.0231]

Wound dressings based on bacterial cellulose (BC) can form a soft and conformable protective layer that can stimulate wound healing while preventing bacteria from entering the wound. Bacteria already present in the wound can, however, thrive in the moist environment created by the BC dressing which can aggravate the healing process. Possibilities to render the BC antimicrobial without affecting the beneficial structural and mechanical properties of the material would hence be highly attractive. Here we present methods for functionalization of BC with epsilon-poly-L-Lysine (epsilon-PLL), a non-toxic biopolymer with broad-spectrum antimicrobial activity. Low molecular weight epsilon-PLL was crosslinked in pristine BC membranes and to carboxymethyl cellulose functionalized BC using carbodiimide chemistry. The functionalization of BC with epsilon-PLL inhibited growth of S. epidermidis on the membranes but did not affect the cytocompatibility to cultured human fibroblasts as compared to native BC. The functionalization had no significant effects on the nanofibrous structure and mechanical properties of the BC. The possibility to functionalize BC with epsilon-PLL is a promising, green and versatile approach to improve the performance of BC in wound care and other biomedical applications. ; Funding Agencies|Linkoping University [2009 00971]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]; Carl Trygger Foundation; Knowledge Foundation

Laminins (LNs) are key components in the extracellular matrix of neuronal tissues in the developing brain and neural stem cell niches. LN-presenting hydrogels can provide a biologically relevant matrix for the 3D culture of neurons toward development of advanced tissue models and cell-based therapies for the treatment of neurological disorders. Biologically derived hydrogels are rich in fragmented LN and are poorly defined concerning composition, which hampers clinical translation. Engineered hydrogels require elaborate and often cytotoxic chemistries for cross-linking and LN conjugation and provide limited possibilities to tailor the properties of the materials. Here a modular hydrogel system for neural 3D cell cultures, based on hyaluronan and poly(ethylene glycol), that is cross-linked and functionalized with human recombinant LN-521 using bioorthogonal copper-free click chemistry, is shown. Encapsulated human neuroblastoma cells demonstrate high viability and grow into spheroids. Long-term neuroepithelial stem cells (lt-NES) cultured in the hydrogels can undergo spontaneous differentiation to neural fate and demonstrate significantly higher viability than cells cultured without LN. The hydrogels further support the structural integrity of 3D bioprinted structures and maintain high viability of bioprinted and syringe extruded lt-NES, which can facilitate biofabrication and development of cell-based therapies. ; Funding Agencies: Swedish Foundation for Strategic Research (SFF) [FFL15-0026]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linköping University [2009-00971]; Carl Tryggers Foundation; Knut and Alice Wallenberg Foundation [KAW 2016.0231, 2020.0206]

The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 alpha beta were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 alpha and beta were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both L- and D-PLNC8 alpha beta caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. The D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, beta 1-22, beta 7-34 and beta 1-20 retained an inhibitory activity. The peptides diffused rapidly (2min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 alpha beta substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 alpha beta is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use. ; Funding Agencies|Foundation of Magnus Bergvalls [2015-00823]; Knowledge Foundation [20150244, 20150086]; Swedish Research CouncilSwedish Research Council [2016-04874, 2017-04475]; Swedish Cancer SocietySwedish Cancer Society [17 0532]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [RMX18-0039]; orebro University

Nanocomposites of metal nanoparticles (NPs) and bacterial nanocellulose (BC) enable fabrication of soft and biocompatible materials for optical, catalytic, electronic, and biomedical applications. Current BC-NP nanocomposites are typically prepared by in situ synthesis of the NPs or electrostatic adsorption of surface functionalized NPs, which limits possibilities to control and tune NP size, shape, concentration, and surface chemistry and influences the properties and performance of the materials. Here a self-assembly strategy is described for fabrication of complex and well-defined BC-NP composites using colloidal gold and silver NPs of different sizes, shapes, and concentrations. The self-assembly process results in nanocomposites with distinct biophysical and optical properties. In addition to antibacterial materials and materials with excellent senor performance, materials with unique mechanoplasmonic properties are developed. The homogenous incorporation of plasmonic gold NPs in the BC enables extensive modulation of the optical properties by mechanical stimuli. Compression gives rise to near-field coupling between adsorbed NPs, resulting in tunable spectral variations and enhanced broadband absorption that amplify both nonlinear optical and thermoplasmonic effects and enables novel biosensing strategies. ; Funding Agencies|Swedish Foundation for Strategic Research (SFF)Swedish Foundation for Strategic Research [FFL15-0026, RMX18-0039]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]; VinnovaVinnova [2016-05156]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [KAW 2016.0231]; Swedish Research CouncilSwedish Research Council [2017-05178, 2015-05002]; Spanish Ministerio de Ciencia, Innovacion y Universidades (MICINN) [MAT2016-77391-R]; Severo Ochoa Centres of Excellence programme - Spanish Research Agency (AEI) [SEV-2017-0706]

Nanocomposites of metal nanoparticles (NPs) and bacterial nanocellulose (BC) enable fabrication of soft and biocompatible materials for optical, catalytic, electronic, and biomedical applications. Current BC–NP nanocomposites are typically prepared by in situ synthesis of the NPs or electrostatic adsorption of surface functionalized NPs, which limits possibilities to control and tune NP size, shape, concentration, and surface chemistry and influences the properties and performance of the materials. Here a self‐assembly strategy is described for fabrication of complex and well‐defined BC–NP composites using colloidal gold and silver NPs of different sizes, shapes, and concentrations. The self‐assembly process results in nanocomposites with distinct biophysical and optical properties. In addition to antibacterial materials and materials with excellent senor performance, materials with unique mechanoplasmonic properties are developed. The homogenous incorporation of plasmonic gold NPs in the BC enables extensive modulation of the optical properties by mechanical stimuli. Compression gives rise to near‐field coupling between adsorbed NPs, resulting in tunable spectral variations and enhanced broadband absorption that amplify both nonlinear optical and thermoplasmonic effects and enables novel biosensing strategies. ; This work was supported by the Swedish Foundation for Strategic Research (SFF) grant no. FFL15‐0026 and framework grant RMX18‐0039 (HEALiX), the Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linköping University (Faculty Grant SFO‐Mat‐LiU no. 2009‐00971), the competence center FunMat‐II that is financially supported by Vinnova (grant no. 2016‐05156), and the Knut and Alice Wallenberg Foundation (grant no. KAW 2016.0231), the Swedish Research Council (grant Nos. 2017‐05178 and 2015‐05002) and the Spanish Ministerio de Ciencia, Innovación y Universidades (MICINN) through the MAT2016‐77391‐R. The ICN2 was supported by the Severo Ochoa Centres of Excellence programme, funded by the Spanish Research Agency (AEI, grant no. SEV‐2017‐0706). ; Peer reviewed