Greta Bergamaschi

Nanomechanics-driven design of synthetic Lipo-EVs: cholesterol tuning recapitulates the biomechanical properties of native EVs, enabling stable biomimetic nanocarriers.

Understanding the mechanisms leading to complex coacervation is a fundamental challenge in biomolecular sciences. Here, we explored the condensation transition and pretransitional behavior of an archetypal system consisting of polyuridylic acid chains (PolyU) and short cationic peptides in buffered aqueous solutions. By combining static and dynamic light scattering with confocal microscopy, we determined the location of the transition and the partitioning of PolyU and peptides between the coexisting phases as a function of the total peptides/PolyU ratio. We find that upon adding peptides in the system, the size of PolyU coils in the single-phase region is progressively reduced by peptide-mediated intrachain bonds. Such conformational constraints become less severe in the dense phase, where part of the bonds become interchain as indicated by the sticky-reptation-type kinetics observed by dynamic light scattering. We propose a phenomenological model in which we include the loss in PolyU conformational entropy induced by peptide decoration and show that this quantity is large enough to be the main driver of the condensation transition. The model well reproduces the observed molecular partitioning between phases. We argue that the role of coil conformational relaxation, here demonstrated for a specific system, might be of general relevance in complex coacervation.

Hydrogels find widespread use in bioapplications for their ability to retain large amounts of water while maintaining structural integrity. In this article we investigate hybrid hydrogels made of nanocellulose and either amino-polyethylenglycol or sodium alginates and we demonstrate two novel results: 1) the biocompatibility of the amino containing hybrid gel synthesized using a simplified receipt that does not require any intermediate synthetic step to functionalize either components and 2) the fact that the fluctuation of the 2nd order correlation function of a Dynamic Light Scattering experiment provides relevant information about the characteristic internal dynamic of the materials across the entire sol-gel transition as well as quantitative information about the ion-specific gel formation. This novel approach offers significantly better temporal (10’s μs) and spatial (10’s μm) resolution than many other state-of-the-art techniques commonly used for such analyses (such as rheometry, SAXS, and NMR) and it might find widespread application in the characterization of the nano to microscale dynamics in soft materials.

A simple route to bio-based cellulose nanofibers (CNF) functionalization is here proposed via noncovalent incorporation of short peptides, enhancing rheology, hydrophobicity, and water vapor barrier properties in CNF-based hydrogels and films.

Supramolecular hydrogels play a pivotal role in many fields of biomedical research, including emerging applications in designing advanced tools for point‐of‐care testing, clinical diagnostics, and lab‐on‐chip analysis. This review outlines the growing relevance of supramolecular hydrogels in biosensing and bioassay devices, highlighting recent advancements that deliver increased sensitivity, real‐time monitoring, and multiplexing capabilities through the distinctive properties of these nanomaterials. Furthermore, the exploration extends to additional applications, such as using hydrogels as three‐dimensional matrices for cell‐based assays.

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive sarcomas that can arise both sporadically and in patients with the genetic syndrome Neurofibromatosis type 1 (NF1). Prognosis is dismal, as large dimensions, risk of relapse, and anatomical localization make surgery poorly effective, and no therapy is known. Hence, the identification of MPNST molecular features that could be hit in an efficient and selective way is mandatory to envision treatment options. Here, we find that MPNSTs express high levels of the glycolytic enzyme Hexokinase 2 (HK2), which is known to shield cancer cells from noxious stimuli when it localizes at MAMs (mitochondria-associated membranes), contact sites between mitochondria and endoplasmic reticulum. A HK2-targeting peptide that dislodges HK2 from MAMs rapidly induces a massive death of MPNST cells. After identifying different matrix metalloproteases (MMPs) expressed in the MPNST microenvironment, we have designed HK2-targeting peptide variants that harbor cleavage sites for these MMPs, making such peptides activatable in the proximity of cancer cells. We find that the peptide carrying the MMP2/9 cleavage site is the most effective, both in inhibiting the in vitro tumorigenicity of MPNST cells and in hampering their growth in mice. Our data indicate that detaching HK2 from MAMs could pave the way for a novel anti-MPNST therapeutic strategy, which could be flexibly adapted to the protease expression features of the tumor microenvironment.

Here we report a proof-of-concept application of a composite Aga-Q3 hydrogel for the gentle confinement and analysis of extracellular vesicles (EVs) on microarray analytical platforms.

Invited for the cover of this issue is the Laboratory of Supramolecular and Bio‐Nanomaterials, coordinated by Pierangelo Metrangolo, at the Politecnico di Milano, Italy. The image depicts the co‐crystal formed by N‐Fmoc‐pentafluorophenylalanine and benzamide, which is also involved in the formation of their mixed hydrogels. Read the full text of the article at 10.1002/chem.202301743.