Encoding Structure in Intrinsically Disordered Protein Biomaterials

Strader, Rachel L.; Shmidov, Yulia; Chilkoti, Ashutosh

doi:10.1021/acs.accounts.3c00624

Cited by 5 publications

(3 citation statements)

References 58 publications

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“…Non-protein moieties such as lipids [200][201][202][203][204] and glycans, [205,206] can be incorporated via posttranslational modifications to introduce additional structural diversity. [69] Integration with ordered inorganic motifs (e. g. apatite nanocrystals) can further be leveraged to direct organicinorganic interactions for supramolecular biofabrication of mineralized structures with exceptional control and hierarchy. [56,207,208] Other opportunities exist for effecting stimulitriggered nanostructure transitions in response to sequential and orthogonal cues.…”

Section: Discussionmentioning

confidence: 99%

“…[93] Furthermore, in such synergistic fusions, coiled coils have been known to improve the mechanical stability or to impart the capacity for hierarchical assembly into nanostructures and hydrogels of IDP-based assemblies. [69,94]…”

Section: Constructs Comprising Helical Ordered Domainsmentioning

confidence: 99%

“…In addition to the precise control over their composition, molecular weight, and monodispersity, noncanonical amino acids can be installed to further expand their chemical functionality. [66,67] While other stimuli such as pH, ionic strength, enzymes, redox, magnetic field can also be used to alter conformational properties of polypeptides, [68] this review focuses on recent reports [4,7,[69][70][71][72] harnessing the thermally triggered assembly behavior of such genetically fused hybrid constructs.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetically Fusing Order‐Promoting and Thermoresponsive Building Blocks to Design Hybrid Biomaterials

Patkar,

Wang,

Mosquera

et al. 2024

Chemistry A European J

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The unique biophysical and biochemical properties of intrinsically disordered proteins (IDPs) and their recombinant derivatives, intrinsically disordered protein polymers (IDPPs) offer opportunities for producing multistimuli‐responsive materials; their sequence‐encoded disorder and tendency for phase separation facilitate the development of multifunctional materials. This review highlights the strategies for enhancing the structural diversity of elastin‐like polypeptides (ELPs) and resilin‐like polypeptides (RLPs), and their self‐assembled structures via genetic fusion to ordered motifs such as helical or beta sheet domains. In particular, this review describes approaches that harness the synergistic interplay between order‐promoting and thermoresponsive building blocks to design hybrid biomaterials, resulting in well‐structured, stimuli‐responsive supramolecular materials ordered on the nanoscale.

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Section: Discussionmentioning

confidence: 99%

Section: Constructs Comprising Helical Ordered Domainsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetically Fusing Order‐Promoting and Thermoresponsive Building Blocks to Design Hybrid Biomaterials

Patkar,

Wang,

Mosquera

et al. 2024

Chemistry A European J

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Engineered Protein Hydrogels as Biomimetic Cellular Scaffolds

Liu,

Gilchrist,

Heilshorn

2024

Advanced Materials

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The biochemical and biophysical properties of the extracellular matrix (ECM) play a pivotal role in regulating cellular behaviors such as proliferation, migration, and differentiation. Engineered protein‐based hydrogels, with highly tunable multifunctional properties, have the potential to replicate key features of the native ECM. Formed by self‐assembly or crosslinking, engineered protein‐based hydrogels can induce a range of cell behaviors through bioactive and functional domains incorporated into the polymer backbone. Using recombinant techniques, the amino acid sequence of the protein backbone can be designed with precise control over the chain‐length, folded structure, and cell‐interaction sites. In this review, the modular design of engineered protein‐based hydrogels from both a molecular‐ and network‐level perspective are discussed, and summarize recent progress and case studies to highlight the diverse strategies used to construct biomimetic scaffolds. This review focuses on amino acid sequences that form structural blocks, bioactive blocks, and stimuli‐responsive blocks designed into the protein backbone for highly precise and tunable control of scaffold properties. Both physical and chemical methods to stabilize dynamic protein networks with defined structure and bioactivity for cell culture applications are discussed. Finally, a discussion of future directions of engineered protein‐based hydrogels as biomimetic cellular scaffolds is concluded.

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Multi-Objective Design of DNA-Stabilized Nanoclusters Using Variational Autoencoders With Automatic Feature Extraction

Sadeghi,

Mastracco,

Gonzàlez-Rosell

et al. 2024

ACS Nano

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DNA-stabilized silver nanoclusters (Ag N -DNAs) have sequence-tuned compositions and fluorescence colors. High-throughput experiments together with supervised machine learning models have recently enabled design of DNA templates that select for Ag N -DNA properties, including near-infrared (NIR) emission that holds promise for deep tissue bioimaging. However, these existing models do not enable simultaneous selection of multiple Ag N -DNA properties, and require significant expert input for feature engineering and class definitions. This work presents a model for multiobjective, continuous-property design of Ag N -DNAs with automatic feature extraction, based on variational autoencoders (VAEs). This model is generative, i.e., it learns both the forward mapping from DNA sequence to Ag N -DNA properties and the inverse mapping from properties to sequence, and is trained on an experimental data set of DNA sequences paired with Ag N -DNA fluorescence properties. Experimental testing shows that the model enables effective design of Ag N -DNA emission, including bright NIR Ag N -DNAs with 4-fold greater abundance compared to training data. In addition, Shapley analysis is employed to discern learned nucleobase patterns that correspond to fluorescence color and brightness. This generative model can be adapted for a range of biomolecular systems with sequence-dependent properties, enabling precise design of emerging biomolecular nanomaterials.

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Encoding Structure in Intrinsically Disordered Protein Biomaterials

Cited by 5 publications

References 58 publications

Genetically Fusing Order‐Promoting and Thermoresponsive Building Blocks to Design Hybrid Biomaterials

Genetically Fusing Order‐Promoting and Thermoresponsive Building Blocks to Design Hybrid Biomaterials

Engineered Protein Hydrogels as Biomimetic Cellular Scaffolds

Multi-Objective Design of DNA-Stabilized Nanoclusters Using Variational Autoencoders With Automatic Feature Extraction

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