Using a Supramolecular Monomer Formulation Approach to Engineer Modular, Dynamic Microgels, and Composite Macrogels.

Microgels show advantages over bulk hydrogels due to convenient control over microgel size and composition, and the ability to use microgels to modularly construct larger hierarchical scaffold hydrogel materials. Here, supramolecular chemistry is used to formulate supramolecular polymer, dynamic microgels solely held together by non-covalent interactions. Four-fold hydrogen bonding ureido-pyrimidinone (UPy) monomers with different functionalities are applied to precisely tune microgel properties in a modular way, via variations in monomer concentration, bifunctional crosslinker ratio, and the incorporation of supramolecular dyes and peptides.

3D Micropatterned Traction Force Microscopy: A Technique to Control 3D Cell Shape While Measuring Cell-Substrate Force Transmission.

Cell shape and function are intimately linked, in a way that is mediated by the forces exerted between cells and their environment. The relationship between cell shape and forces has been extensively studied for cells seeded on flat 2D substrates, but not for cells in more physiological 3D settings. Here, a technique called 3D micropatterned traction force microscopy (3D-µTFM) to confine cells in 3D wells of defined shape, while simultaneously measuring the forces transmitted between cells and their microenvironment is demonstrated.

Substrate stiffness-dependent activation of Hippo pathway in cancer associated fibroblasts.

The tumor microenvironment (TME) comprises a heterogenous cell population within a complex three-dimensional (3D) extracellular matrix (ECM). Stromal cells within this TME are altered by signaling cues from cancer cells to support uncontrolled tumor growth and invasion events. Moreover, the ECM also plays a fundamental role in tumor development through pathological remodeling, stiffening and interaction with TME cells.

Light-Activated Agonist-Potentiator of GABA Receptors for Reversible Neuroinhibition in Wildtype Mice.

Gamma aminobutyric acid type A receptors (GABARs) play a key role in the mammalian central nervous system (CNS) as drivers of neuroinhibitory circuits, which are commonly targeted for therapeutic purposes with potentiator drugs. However, due to their widespread expression and strong inhibitory action, systemic pharmaceutical potentiation of GABARs inevitably causes adverse effects regardless of the drug selectivity. Therefore, therapeutic guidelines must often limit or exclude clinically available GABAR potentiators, despite their high efficacy, good biodistribution, and favorable molecular properties.

Evaluation of the electrochemical response of aromatic peptides for biodetection of dopamine.

Biologically inspired aromatic peptide-based materials are gaining increasing interest as novel charge transport materials for bioelectronics due to their remarkable electrical response and inherent biocompatibility. In this work, the electrochemical response of ten aromatic amino acids and eleven aromatic peptides has been evaluated to assess the potential of incorporating peptides into electrochemical sensors not as biorecognition elements but as biocompatible electronic materials. While the electrochemical response of amino acids is null in all cases, the hexapeptide of phenylalanine (Phe) capped with eight polyethylene glycol units at the N-terminus and, especially, the cyclic dipeptide formed by two dehydro-phenylalanine residues (cyclo(ΔPhe)), which organize in fibrillary self-assembled structures of nano- and submicrometric size, respectively, are the most electroactive peptides.

Antibacterial and cytocompatible silver coating for titanium Boston Keratoprosthesis.

The Boston Keratoprosthesis (BKPro) serves as a medical solution for restoring vision in complex cases of corneal blindness. Comprising a front plate made of polymethylmethacrylate (PMMA) and a back plate of titanium (Ti), this device utilizes the beneficial biomaterial properties of Ti. While BKPro demonstrates promising retention rates, infection emerges as a significant concern that impacts its long-term efficacy.

3D Printing as a Strategy to Scale-Up Biohybrid Hydrogels for T Cell Manufacture.

The emergence of cellular immunotherapy treatments is introducing more efficient strategies to combat cancer as well as autoimmune and infectious diseases. However, the cellular manufacturing procedures associated with these therapies remain costly and time-consuming, thus limiting their applicability. Recently, lymph-node-inspired PEG-heparin hydrogels have been demonstrated to improve primary human T cell culture at the laboratory scale.

The cellular prion protein does not affect tau seeding and spreading of sarkosyl-insoluble fractions from Alzheimer's disease.

The cellular prion protein (PrP) plays many roles in the developing and adult brain. In addition, PrP binds to several amyloids in oligomeric and prefibrillar forms and may act as a putative receptor of abnormal misfolded protein species. The role of PrP in tau seeding and spreading is not known.

Swarms of Enzymatic Nanobots for Efficient Gene Delivery.

This study investigates the synthesis and optimization of nanobots (NBs) loaded with pDNA using the layer-by-layer (LBL) method and explores the impact of their collective motion on the transfection efficiency. NBs consist of biocompatible and biodegradable poly(lactic--glycolic acid) (PLGA) nanoparticles and are powered by the urease enzyme, enabling autonomous movement and collective swarming behavior. experiments were conducted to validate the delivery efficiency of fluorescently labeled NBs, using two-dimensional (2D) and three-dimensional (3D) cell models: murine urothelial carcinoma cell line (MB49) and spheroids from human urothelial bladder cancer cells (RT4).

Combining three-dimensionality and CaP glass-PLA composites: Towards an efficient vascularization in bone tissue healing.

Bone regeneration often fails due to implants/grafts lacking vascular supply, causing necrotic tissue and poor integration. Microsurgical techniques are used to overcome this issue, allowing the graft to anastomose. These techniques have limitations, including severe patient morbidity and current research focuses on stimulating angiogenesis in situ using growth factors, presenting limitations, such as a lack of control and increased costs.

Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M Receptor.

The field of G protein-coupled receptor (GPCR) research has greatly benefited from the spatiotemporal resolution provided by light controllable, i.e., photoswitchable ligands.

Photoelectrochemical Two-Dimensional Electronic Spectroscopy (PEC2DES) of Photosystem I: Charge Separation Dynamics Hidden in a Multichromophoric Landscape.

We present a nonlinear spectroelectrochemical technique to investigate photosynthetic protein complexes. The PEC2DES setup combines photoelectrochemical detection (PEC) that selectively probes the protein photogenerated charges output with two-dimensional electronic spectroscopy (2DES) excitation that spreads the nonlinear optical response of the system in an excitation-detection map. PEC allows us to distinguish the contribution of charge separation (CS) from other de-excitation pathways, whereas 2DES allows us to disentangle congested spectral bands and evaluate the exciton dynamics (decays and coherences) of the photosystem complex.

Nucleocytoplasmic transport senses mechanical forces independently of cell density in cell monolayers.

Cells sense and respond to mechanical forces through mechanotransduction, which regulates processes in health and disease. In single adhesive cells, mechanotransduction involves the transmission of force from the extracellular matrix to the cell nucleus, where it affects nucleocytoplasmic transport (NCT) and the subsequent nuclear localization of transcriptional regulators, such as YAP (also known as YAP1). However, if and how NCT is mechanosensitive in multicellular systems is unclear.

An In Vitro Model of the Blood-Brain Barrier for the Investigation and Isolation of the Key Drivers of Barriergenesis.

The blood-brain barrier (BBB) tightly regulates substance transport between the bloodstream and the brain. Models for the study of the physiological processes affecting the BBB, as well as predicting the permeability of therapeutic substances for neurological and neurovascular pathologies, are highly desirable. Existing models, such as Transwell utilizing-models, do not mimic the extracellular environment of the BBB with their stiff, semipermeable, non-biodegradable membranes.

Quality assessment of regenerated bone in intraosseous and intramuscular scaffolds by spectroscopy and nanoindentation.

The efficiency of synthetic bone grafts can be evaluated either in osseous sites, to analyze osteoconduction or ectopically, in intramuscular or subcutaneous sites, to assess osteoinduction. Bone regeneration is usually evaluated in terms of the presence and quantity of newly formed bone, but little information is normally provided on the quality of this bone. Here, we propose a novel approach to evaluate bone quality by the combined use of spectroscopy techniques and nanoindentation.

Massively parallel genetic perturbation reveals the energetic architecture of an amyloid beta nucleation reaction.

Amyloid protein aggregates are pathological hallmarks of more than fifty human diseases but how soluble proteins nucleate to form amyloids is poorly understood. Here we use combinatorial mutagenesis, a kinetic selection assay, and machine learning to massively perturb the energetics of the nucleation reaction of amyloid beta (Aβ42), the protein that aggregates in Alzheimer's disease. In total, we quantify the nucleation rates of >140,000 variants of Aβ42.

Steps Toward Recapitulating Endothelium: A Perspective on the Next Generation of Hemocompatible Coatings.

Endothelium, the lining in this blood vessel, orchestrates three main critical functions such as protecting blood components, modulating of hemostasis by secreting various inhibitors, and directing clot digestion (fibrinolysis) by activating tissue plasminogen activator. No other surface can perform these tasks; thus, the contact of blood and blood-contacting medical devices inevitably leads to the activation of coagulation, often causing device failure, and thromboembolic complications. This perspective, first, discusses the biological mechanisms of activation of coagulation and highlights the efforts of advanced coatings to recapitulate one characteristic of endothelium, hereafter single functions of endothelium and noting necessity of the synergistic integration of its three main functions.

Massive experimental quantification of amyloid nucleation allows interpretable deep learning of protein aggregation.

Protein aggregation is a pathological hallmark of more than fifty human diseases and a major problem for biotechnology. Methods have been proposed to predict aggregation from sequence, but these have been trained and evaluated on small and biased experimental datasets. Here we directly address this data shortage by experimentally quantifying the amyloid nucleation of >100,000 protein sequences.

Supramolecular Motion Enables Chondrogenic Bioactivity of a Cyclic Peptide Mimetic of Transforming Growth Factor-β1.

Transforming growth factor (TGF)-β1 is a multifunctional protein that is essential in many cellular processes that include fibrosis, inflammation, chondrogenesis, and cartilage repair. In particular, cartilage repair is important to avoid physical disability since this tissue does not have the inherent capacity to regenerate beyond full development. We report here on supramolecular coassemblies of two peptide amphiphile molecules, one containing a TGF-β1 mimetic peptide, and another which is one of two constitutional isomers lacking bioactivity.