Trends in the design and use of elastin-like recombinamers as biomaterials.

Elastin-like recombinamers (ELRs), which derive from one of the repetitive domains found in natural elastin, have been intensively studied in the last few years from several points of view. In this mini review, we discuss all the recent works related to the investigation of ELRs, starting with those that define these polypeptides as model intrinsically disordered proteins or regions (IDPs or IDRs) and its relevance for some biomedical applications. Furthermore, we summarize the current knowledge on the development of drug, vaccine and gene delivery systems based on ELRs, while also emphasizing the use of ELR-based hydrogels in tissue engineering and regenerative medicine (TERM). Finally, we show different studies that explore applications in other fields, and several examples that describe biomaterial blends in which ELRs have a key role. This review aims to give an overview of the recent advances regarding ELRs and to encourage further investigation of their properties and applications.

[1]  M. Bonn,et al.  Genetically encoded lipid–polypeptide hybrid biomaterials that exhibit temperature-triggered hierarchical self-assembly , 2018, Nature Chemistry.

[2]  A. Gaggar,et al.  Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection , 2015, Nature Communications.

[3]  E. Beniash,et al.  Structural Changes in Amelogenin upon Self-assembly and Mineral Interactions , 2012, Journal of dental research.

[4]  A. Weiss,et al.  Fabricated Elastin , 2015, Advanced healthcare materials.

[5]  Ashutosh Chilkoti,et al.  Applications of elastin-like polypeptides in tissue engineering. , 2010, Advanced drug delivery reviews.

[6]  S. Heilshorn,et al.  Tuning Bulk Hydrogel Degradation by Simultaneous Control of Proteolytic Cleavage Kinetics and Hydrogel Network Architecture. , 2018, ACS macro letters.

[7]  Peter Tompa,et al.  Structure and Function of Intrinsically Disordered Proteins , 2009 .

[8]  Fulin Chen,et al.  Novel hemostatic biomolecules based on elastin-like polypeptides and the self-assembling peptide RADA-16 , 2018, BMC Biotechnology.

[9]  Fan Yang,et al.  Elastin-like protein-hyaluronic acid (ELP-HA) hydrogels with decoupled mechanical and biochemical cues for cartilage regeneration. , 2017, Biomaterials.

[10]  J. Champion,et al.  Thermally triggered self-assembly of folded proteins into vesicles. , 2014, Journal of the American Chemical Society.

[11]  Bart Landuyt,et al.  Vascular Endothelial Growth Factor and Angiogenesis , 2004, Pharmacological Reviews.

[12]  A. Khademhosseini,et al.  A Highly Elastic and Rapidly Crosslinkable Elastin‐Like Polypeptide‐Based Hydrogel for Biomedical Applications , 2015, Advanced functional materials.

[13]  Wilfred Chen,et al.  SpyTag/SpyCatcher Functionalization of E2 Nanocages with Stimuli-Responsive Z-ELP Affinity Domains for Tunable Monoclonal Antibody Binding and Precipitation Properties. , 2018, Bioconjugate chemistry.

[14]  L. Sandberg,et al.  Molecular Model for Elastin Structure and Function , 1973, Nature.

[15]  L. Setton,et al.  Fusion order controls expression level and activity of elastin‐like polypeptide fusion proteins , 2009, Protein science : a publication of the Protein Society.

[16]  D. Urry,et al.  Synthetic, cross-linked polypentapeptide fo tropoelastin: an anisotropic, fibrillar elastomer. , 1976, Biochemistry.

[17]  V. Uversky The alphabet of intrinsic disorder , 2013, Intrinsically disordered proteins.

[18]  M. Yarmush,et al.  The development and characterization of SDF1α-elastin-like-peptide nanoparticles for wound healing. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[19]  Ovijit Chaudhuri,et al.  Maintenance of Neural Progenitor Cell Stemness in 3D Hydrogels Requires Matrix Remodeling , 2017, Nature materials.

[20]  Joseph J Kim,et al.  Vascularization of three-dimensional engineered tissues for regenerative medicine applications. , 2016, Acta biomaterialia.

[21]  R. Hancock,et al.  Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies , 2006, Nature Biotechnology.

[22]  Matthew B. Kubilius,et al.  Protein Engineered Triblock Polymers Composed of Two SADs: Enhanced Mechanical Properties and Binding Abilities. , 2018, Biomacromolecules.

[23]  F. Arnold,et al.  Synthesis of bioactive protein hydrogels by genetically encoded SpyTag-SpyCatcher chemistry , 2014, Proceedings of the National Academy of Sciences.

[24]  J. Champion,et al.  Two-step protein self-assembly in the extracellular matrix. , 2013, Angewandte Chemie.

[25]  Wenwen Huang,et al.  Computational smart polymer design based on elastin protein mutability. , 2017, Biomaterials.

[26]  Ashutosh Chilkoti,et al.  Convergence of Artificial Protein Polymers and Intrinsically Disordered Proteins. , 2018, Biochemistry.

[27]  J. Hubbell,et al.  Vascular endothelial cell adhesion and spreading promoted by the peptide REDV of the IIICS region of plasma fibronectin is mediated by integrin alpha 4 beta 1. , 1992, The Journal of biological chemistry.

[28]  J. Rodríguez‐Cabello,et al.  Biocompatible ELR-Based Polyplexes Coated with MUC1 Specific Aptamers and Targeted for Breast Cancer Gene Therapy. , 2016, Molecular pharmaceutics.

[29]  J. Rodríguez‐Cabello,et al.  A transferrin receptor-binding mucoadhesive elastin-like recombinamer: In vitro and in vivo characterization. , 2019, Acta biomaterialia.

[30]  H. Gill,et al.  Synthesis and Immunogenicity Assessment of Elastin-Like Polypeptide-M2e Construct as an Influenza Antigen. , 2014, Nano LIFE.

[31]  A. Mata,et al.  Mineralization and bone regeneration using a bioactive elastin-like recombinamer membrane. , 2014, Biomaterials.

[32]  J. Rodríguez‐Cabello,et al.  Amphiphilic Elastin-Like Block Co-Recombinamers Containing Leucine Zippers: Cooperative Interplay between Both Domains Results in Injectable and Stable Hydrogels. , 2015, Biomacromolecules.

[33]  A. Fok,et al.  Biomimetic Mineralization of Recombinamer-Based Hydrogels toward Controlled Morphologies and High Mineral Density. , 2015, ACS applied materials & interfaces.

[34]  J. Rodríguez‐Cabello,et al.  Efficient cell and cell-sheet harvesting based on smart surfaces coated with a multifunctional and self-organizing elastin-like recombinamer. , 2013, Biomacromolecules.

[35]  J. Rodríguez‐Cabello,et al.  Elastin-like polypeptides in drug delivery. , 2016, Advanced drug delivery reviews.

[36]  Jonathan R. McDaniel,et al.  Genetically Encoding Albumin Binding into Chemotherapeutic-loaded Polypeptide Nanoparticles Enhances Their Antitumor Efficacy. , 2018, Nano letters.

[37]  J. Smeitink,et al.  Octa‐arginine boosts the penetration of elastin‐like polypeptide nanoparticles in 3D cancer models , 2019, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[38]  Rui L. Reis,et al.  Co-assembly, spatiotemporal control and morphogenesis of a hybrid protein-peptide system. , 2015, Nature chemistry.

[39]  M. Howarth,et al.  Assembling and decorating hyaluronan hydrogels with twin protein superglues to mimic cell-cell interactions. , 2018, Biomaterials.

[40]  M. Alonso,et al.  Elastin-like recombinamer catalyst-free click gels: characterization of poroelastic and intrinsic viscoelastic properties. , 2014, Acta biomaterialia.

[41]  K. Kiick,et al.  Noncovalent Modulation of the Inverse Temperature Transition and Self-Assembly of Elastin-b-Collagen-like Peptide Bioconjugates. , 2015, Journal of the American Chemical Society.

[42]  J. Rodríguez‐Cabello,et al.  Spatial control and cell adhesion selectivity on model gold surfaces grafted with elastin-like recombinamers , 2018, European Polymer Journal.

[43]  A. Chilkoti,et al.  Expression and purification of recombinant proteins from Escherichia coli: Comparison of an elastin‐like polypeptide fusion with an oligohistidine fusion , 2004, Protein science : a publication of the Protein Society.

[44]  H. Gill,et al.  Generation of induced pluripotent stem cells using elastin like polypeptides as a non-viral gene delivery system. , 2020, Biochimica et biophysica acta. Molecular basis of disease.

[45]  A. Ibáñez-Fonseca,et al.  Bioactive scaffolds based on elastin‐like materials for wound healing , 2018, Advanced drug delivery reviews.

[46]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[47]  J. Rodríguez‐Cabello,et al.  Recombinant Technology in the Development of Materials and Systems for Soft‐Tissue Repair , 2015, Advanced healthcare materials.

[48]  F. Sánchez-Guijo,et al.  Biocompatibility of two model elastin‐like recombinamer‐based hydrogels formed through physical or chemical cross‐linking for various applications in tissue engineering and regenerative medicine , 2018, Journal of tissue engineering and regenerative medicine.

[49]  Yaroslava G. Yingling,et al.  Molecular description of the LCST behavior of an elastin-like polypeptide. , 2014, Biomacromolecules.

[50]  S. Gharib,et al.  Matrix metalloproteinases in emphysema. , 2018, Matrix biology : journal of the International Society for Matrix Biology.

[51]  M. Muthukumar,et al.  Artificial Protein Block Copolymers Blocks Comprising Two Distinct Self‐Assembling Domains , 2009, Chembiochem : a European journal of chemical biology.

[52]  J. Rodríguez‐Cabello,et al.  Combining Catalyst-Free Click Chemistry with Coaxial Electrospinning to Obtain Long-Term, Water-Stable, Bioactive Elastin-Like Fibers for Tissue Engineering Applications. , 2018, Macromolecular bioscience.

[53]  J. Rodríguez‐Cabello,et al.  Intrafibrillar Mineralization of Self-Assembled Elastin-Like Recombinamer Fibrils. , 2017, ACS applied materials & interfaces.

[54]  F Javier Arias,et al.  Emerging applications of multifunctional elastin-like recombinamers. , 2011, Nanomedicine.

[55]  A. Mata,et al.  Protein disorder–order interplay to guide the growth of hierarchical mineralized structures , 2018, Nature Communications.

[56]  M. Pihl,et al.  Antibiofilm elastin-like polypeptide coatings: functionality, stability, and selectivity. , 2019, Acta biomaterialia.

[57]  M. T. Neves-Petersen,et al.  Development of elastin-like recombinamer films with antimicrobial activity. , 2015, Biomacromolecules.

[58]  Tsuyoshi Murata,et al.  {m , 1934, ACML.

[59]  Lukasz A. Kurgan,et al.  D2P2: database of disordered protein predictions , 2012, Nucleic Acids Res..

[60]  A. Chilkoti,et al.  Fusion of fibroblast growth factor 21 to a thermally responsive biopolymer forms an injectable depot with sustained anti‐diabetic action , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[61]  Julie C. Liu,et al.  A bioinspired elastin-based protein for a cytocompatible underwater adhesive. , 2017, Biomaterials.

[62]  E. Wright,et al.  Engineering Globular Protein Vesicles through Tunable Self-Assembly of Recombinant Fusion Proteins. , 2017, Small.

[63]  A. Schreiber,et al.  Designer amphiphilic proteins as building blocks for the intracellular formation of organelle-like compartments. , 2015, Nature materials.

[64]  Sarah Rauscher,et al.  Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. , 2006, Structure.

[65]  J. Rodríguez‐Cabello,et al.  Formation of calcium phosphate nanostructures under the influence of self-assembling hybrid elastin-like-statherin recombinamers , 2016 .

[66]  Jonathan R. McDaniel,et al.  A unified model for de novo design of elastin-like polypeptides with tunable inverse transition temperatures. , 2013, Biomacromolecules.

[67]  Timothy D. Craggs,et al.  Phase Transition of a Disordered Nuage Protein Generates Environmentally Responsive Membraneless Organelles , 2015, Molecular cell.

[68]  R. Machado,et al.  Production of bioactive hepcidin by recombinant DNA tagging with an elastin-like recombinamer. , 2018, New biotechnology.

[69]  Guilin Wang,et al.  Enhancing Pharmacokinetics, Tumor Accumulation, and Antitumor Efficacy by Elastin‐Like Polypeptide Fusion of Interferon Alpha , 2015, Advanced materials.

[70]  O. Klein,et al.  Intrinsically disordered proteins drive enamel formation via an evolutionarily conserved self-assembly motif , 2017, Proceedings of the National Academy of Sciences.

[71]  F Javier Arias,et al.  Immunomodulatory nanoparticles from elastin-like recombinamers: single-molecules for tuberculosis vaccine development. , 2013, Molecular pharmaceutics.

[72]  W. Morrison,et al.  In Vitro and In Vivo Approaches for Pre-vascularization of 3-Dimensional Engineered Tissues , 2017 .

[73]  P ? ? ? ? ? ? ? % ? ? ? ? , 1991 .

[74]  M. Marquet,et al.  Genetic Engineering of Structural Protein Polymers , 1990, Biotechnology progress.

[75]  A. Boskey,et al.  Intrinsically disordered proteins and biomineralization. , 2016, Matrix biology : journal of the International Society for Matrix Biology.

[76]  J. Rodríguez‐Cabello,et al.  “Recombinamers” as advanced materials for the post-oil age , 2009 .

[77]  A. Chilkoti,et al.  Creating cellular patterns using genetically engineered, gold- and cell-binding polypeptides. , 2016, Biointerphases.

[78]  F. O'Brien,et al.  Investigating the interplay between substrate stiffness and ligand chemistry in directing mesenchymal stem cell differentiation within 3D macro-porous substrates. , 2018, Biomaterials.

[79]  D. Tirrell,et al.  Genetic Engineering of Polymeric Materials , 1991 .

[80]  Erin G Roberts,et al.  Fabrication and Characterization of Recombinant Silk-Elastin-Like-Protein (SELP) Fiber. , 2018, Macromolecular bioscience.

[81]  R. Raines,et al.  Chemical synthesis of proteins. , 2005, Annual review of biophysics and biomolecular structure.

[82]  J. Rodríguez‐Cabello,et al.  Tethering QK peptide to enhance angiogenesis in elastin-like recombinamer (ELR) hydrogels , 2019, Journal of Materials Science: Materials in Medicine.

[83]  K. Kiick,et al.  Self-Assembly of Stable Nanoscale Platelets from Designed Elastin-like Peptide-Collagen-like Peptide Bioconjugates. , 2019, Biomacromolecules.

[84]  M. Pastuszka,et al.  Flipping the Switch on Clathrin‐Mediated Endocytosis using Thermally Responsive Protein Microdomains , 2014, Advanced functional materials.

[85]  D. Urry,et al.  Studies on the conformation and interactions of elastin secondary structure of synthetic repeat hexapeptides. , 1975, Biochimica et biophysica acta.

[86]  D. Gowda,et al.  Cell adhesion and growth on synthetic elastomeric matrices containing Arg-Gly-Asp-Ser-3. , 1992, Journal of biomedical materials research.

[87]  R. Pappu,et al.  Injectable tissue integrating networks from recombinant polypeptides with tunable order , 2018, Nature Materials.

[88]  Expression and Purification of Neurotrophin-Elastin-Like Peptide Fusion Proteins for Neural Regeneration , 2016, BioDrugs.

[89]  Shigehiko Suzuki,et al.  The development of a novel wound healing material, silk-elastin sponge , 2017, Journal of biomaterials science. Polymer edition.

[90]  Malav S Desai,et al.  Self-Healing Elastin-Bioglass Hydrogels. , 2016, Biomacromolecules.

[91]  K. Kiick,et al.  Effect of Peptide Sequence on the LCST-Like Transition of Elastin-Like Peptides and Elastin-Like Peptide-Collagen-Like Peptide Conjugates: Simulations and Experiments. , 2019, Biomacromolecules.

[92]  T. Schmitz-Rode,et al.  Macroporous click-elastin-like hydrogels for tissue engineering applications. , 2018, Materials science & engineering. C, Materials for biological applications.

[93]  C. García-Arévalo,et al.  Rapid micropatterning by temperature-triggered reversible gelation of a recombinant smart elastin-like tetrablock-copolymer , 2010 .

[94]  Wen‐Bin Zhang,et al.  Supporting Information for Programming molecular association and viscoelastic behavior in protein networks , 2016 .

[95]  Annika Enejder,et al.  Hybrid Elastin-like Polypeptide–Polyethylene Glycol (ELP-PEG) Hydrogels with Improved Transparency and Independent Control of Matrix Mechanics and Cell Ligand Density , 2014, Biomacromolecules.

[96]  Jeffrey M. Caves,et al.  Microablation of collagen-based substrates for soft tissue engineering , 2014, Biomedical materials.

[97]  M. Madan Babu,et al.  The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease , 2016, Biochemical Society transactions.

[98]  R. Mecham Elastin in lung development and disease pathogenesis. , 2018, Matrix biology : journal of the International Society for Matrix Biology.

[99]  J. Rodríguez‐Cabello,et al.  * Bone Regeneration Mediated by a Bioactive and Biodegradable Extracellular Matrix-Like Hydrogel Based on Elastin-Like Recombinamers. , 2017, Tissue engineering. Part A.

[100]  J. Rodríguez‐Cabello,et al.  Elastin-like recombinamers with acquired functionalities for gene-delivery applications. , 2015, Journal of biomedical materials research. Part A.

[101]  J. Camarero,et al.  Recombinant expression of backbone‐cyclized polypeptides , 2013, Biopolymers.

[102]  J. West,et al.  Vascularization of engineered tissues: approaches to promote angio-genesis in biomaterials. , 2008, Current topics in medicinal chemistry.

[103]  J. Rodríguez‐Cabello,et al.  Self-organized ECM-mimetic model based on an amphiphilic multiblock silk-elastin-like corecombinamer with a concomitant dual physical gelation process. , 2014, Biomacromolecules.

[104]  Lei Cai,et al.  One-pot Synthesis of Elastin-like Polypeptide Hydrogels with Grafted VEGF-Mimetic Peptides. , 2014, Biomaterials science.

[105]  Mark G Allen,et al.  Generation of Spatially Aligned Collagen Fiber Networks Through Microtransfer Molding , 2014, Advanced healthcare materials.

[106]  M. Textor,et al.  A bioactive elastin-like recombinamer reduces unspecific protein adsorption and enhances cell response on titanium surfaces. , 2014, Colloids and surfaces. B, Biointerfaces.

[107]  Michael S Valic,et al.  Angiogenic Biomaterials to Promote Tissue Vascularization and Integration , 2013 .

[108]  F. Arias,et al.  Self-Assembling Elastin-Like Hydrogels for Timolol Delivery: Development of an Ophthalmic Formulation Against Glaucoma. , 2017, Molecular pharmaceutics.

[109]  Wenwen Huang,et al.  Design of Multistimuli Responsive Hydrogels Using Integrated Modeling and Genetically Engineered Silk–Elastin‐Like Proteins , 2016, Advanced functional materials.

[110]  Aggregation behaviour of biohybrid microgels from elastin-like recombinamers. , 2016, Soft matter.

[111]  A. Taubert,et al.  Recombinant DNA technology and click chemistry: a powerful combination for generating a hybrid elastin-like-statherin hydrogel to control calcium phosphate mineralization , 2017, Beilstein journal of nanotechnology.

[112]  J. Planell,et al.  3D silicon doped hydroxyapatite scaffolds decorated with Elastin-like Recombinamers for bone regenerative medicine. , 2016, Acta biomaterialia.

[113]  A. Chilkoti,et al.  Long circulating genetically encoded intrinsically disordered zwitterionic polypeptides for drug delivery. , 2019, Biomaterials.

[114]  J. Blanco,et al.  Regeneration of hyaline cartilage promoted by xenogeneic mesenchymal stromal cells embedded within elastin-like recombinamer-based bioactive hydrogels , 2017, Journal of Materials Science: Materials in Medicine.

[115]  F. Simmel,et al.  Towards synthetic cells using peptide-based reaction compartments , 2018, Nature Communications.

[116]  Eric W. Roth,et al.  Artificial protein block polymer libraries bearing two SADs: effects of elastin domain repeats. , 2011, Biomacromolecules.

[117]  Carolyn E. Mills,et al.  Elastin-like Polypeptide (ELP) Charge Influences Self-Assembly of ELP-mCherry Fusion Proteins. , 2018, Biomacromolecules.

[118]  Ali Khademhosseini,et al.  Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static Networks. , 2016, Trends in biotechnology.

[119]  C. Morrow,et al.  Production and Purification of a Recombinant Elastomeric Polypeptide, G‐(VPGVG)19‐VPGV, from Escherichia coli , 1992, Biotechnology progress.

[120]  R. Pappu,et al.  Advances in Understanding Stimulus-Responsive Phase Behavior of Intrinsically Disordered Protein Polymers. , 2018, Journal of molecular biology.

[121]  Wilfred Chen,et al.  Ligand-Induced Cross-Linking of Z-Elastin-like Polypeptide-Functionalized E2 Protein Nanoparticles for Enhanced Affinity Precipitation of Antibodies. , 2017, Biomacromolecules.

[122]  Kyle J Isaacson,et al.  Self-Assembly of Thermoresponsive Recombinant Silk-Elastinlike Nanogels. , 2017, Macromolecular bioscience.

[123]  V. Renugopalakrishnan,et al.  Proton magnetic resonance and conformational energy calculations of repeat peptides of tropoelastin. A permutation of the hexapeptide. , 1978, Biochimica et biophysica acta.

[124]  J. Rodríguez‐Cabello,et al.  PHBV wet-spun scaffold coated with ELR-REDV improves vascularization for bone tissue engineering , 2018, Biomedical materials.

[125]  E Ruoslahti,et al.  RGD and other recognition sequences for integrins. , 1996, Annual review of cell and developmental biology.

[126]  Diana M. Mitrea,et al.  Coexisting Liquid Phases Underlie Nucleolar Subcompartments , 2016, Cell.

[127]  S. Heilshorn,et al.  Dynamic, 3D‐Pattern Formation Within Enzyme‐Responsive Hydrogels , 2009 .

[128]  J. Rodríguez‐Cabello,et al.  Förster Resonance Energy Transfer-Paired Hydrogel Forming Silk-Elastin-Like Recombinamers by Recombinant Conjugation of Fluorescent Proteins. , 2017, Bioconjugate chemistry.

[129]  X. He,et al.  Direct loading of CTL epitopes onto MHC class I complexes on dendritic cell surface in vivo. , 2018, Biomaterials.

[130]  J. Rodríguez‐Cabello,et al.  Cartilage Regeneration in Preannealed Silk Elastin-Like Co-Recombinamers Injectable Hydrogel Embedded with Mature Chondrocytes in an Ex Vivo Culture Platform. , 2018, Biomacromolecules.

[131]  J. Rodríguez‐Cabello,et al.  Use of proteolytic sequences with different cleavage kinetics as a way to generate hydrogels with preprogrammed cell-infiltration patterns imparted over their given 3D spatial structure , 2019, Biofabrication.

[132]  Carolyn E. Mills,et al.  Effect of ELP Sequence and Fusion Protein Design on Concentrated Solution Self-Assembly. , 2016, Biomacromolecules.

[133]  Anita J. Hill,et al.  Structural ensembles reveal intrinsic disorder for the multi-stimuli responsive bio-mimetic protein Rec1-resilin , 2015, Scientific Reports.

[134]  J. Rodríguez‐Cabello,et al.  Nanotechnological Approaches to Therapeutic Delivery Using Elastin-Like Recombinamers. , 2015, Bioconjugate chemistry.

[135]  Alvaro Mata,et al.  Cross-linking of a biopolymer-peptide co-assembling system. , 2017, Acta biomaterialia.

[136]  T. Yamaoka,et al.  In vivo guided vascular regeneration with a non-porous elastin-like polypeptide hydrogel tubular scaffold. , 2017, Journal of biomedical materials research. Part A.

[137]  S. Heilshorn,et al.  Tyrosine-Selective Functionalization for Bio-Orthogonal Cross-Linking of Engineered Protein Hydrogels. , 2017, Bioconjugate chemistry.

[138]  Markus J Buehler,et al.  Unraveling the Molecular Mechanisms of Thermo-responsive Properties of Silk-Elastin-Like Proteins by Integrating Multiscale Modeling and Experiment. , 2018, Journal of materials chemistry. B.

[139]  J. Rodríguez‐Cabello,et al.  Random and oriented electrospun fibers based on a multicomponent, in situ clickable elastin-like recombinamer system for dermal tissue engineering. , 2018, Acta biomaterialia.

[140]  Lisa D. Muiznieks,et al.  Direct observation of structure and dynamics during phase separation of an elastomeric protein , 2017, Proceedings of the National Academy of Sciences.

[141]  A. Doherty,et al.  Viral Vectors: The Road to Reducing Genotoxicity. , 2017, Toxicological sciences : an official journal of the Society of Toxicology.

[142]  G. Christofori,et al.  Polyethylenimine (PEI) is a simple, inexpensive and effective reagent for condensing and linking plasmid DNA to adenovirus for gene delivery , 1997, Gene Therapy.

[143]  M. Alonso,et al.  Control of angiogenesis and host response by modulating the cell adhesion properties of an Elastin-Like Recombinamer-based hydrogel. , 2017, Biomaterials.

[144]  John B. Shoven,et al.  I , Edinburgh Medical and Surgical Journal.

[145]  J. Rodríguez‐Cabello,et al.  Elastin-like recombinamer-covered stents: Towards a fully biocompatible and non-thrombogenic device for cardiovascular diseases. , 2015, Acta biomaterialia.

[146]  V. Uversky Intrinsically disordered proteins and their (disordered) proteomes in neurodegenerative disorders , 2015, Front. Aging Neurosci..

[147]  A. Chilkoti,et al.  Elastin‐like polypeptides as models of intrinsically disordered proteins , 2015, FEBS letters.

[148]  R. Neubert,et al.  Molecular-level characterization of elastin-like constructs and human aortic elastin. , 2014, Matrix biology : journal of the International Society for Matrix Biology.

[149]  Elliot L Chaikof,et al.  Acellular vascular grafts generated from collagen and elastin analogs. , 2013, Acta biomaterialia.

[150]  H. Dyson,et al.  Intrinsically disordered proteins in cellular signalling and regulation , 2014, Nature Reviews Molecular Cell Biology.

[151]  V. Uversky Natively unfolded proteins: A point where biology waits for physics , 2002, Protein science : a publication of the Protein Society.

[152]  C. Aparicio,et al.  Hybrid Nanotopographical Surfaces Obtained by Biomimetic Mineralization of Statherin‐Inspired Elastin‐Like Recombinamers , 2014, Advanced healthcare materials.

[153]  J. Correia,et al.  Modeling the Early Stages of Phase Separation in Disordered Elastin-like Proteins. , 2018, Biophysical journal.

[154]  Dan W. Urry,et al.  What Sustains Life?: Consilient Mechanisms for Protein-Based Machines and Materials , 2006 .