Advancing Artificial Cells with Functional Compartmentalized Polymeric Systems - In Honor of Wolfgang Meier.

The fundamental building block of living organisms is the cell, which is the universal biological base of all living entities. This micrometric mass of cytoplasm and the membrane border have fascinated scientists due to the highly complex and multicompartmentalized structure. This specific organization enables numerous metabolic reactions to occur simultaneously and in segregated spaces, without disturbing each other, but with a promotion of inter- and intracellular communication of biomolecules.

Toward Synthetic Intrinsically Disordered Polypeptides (IDPs): Controlled Incorporation of Glycine in the Ring-Opening Polymerization of -Carboxyanhydrides.

Intrinsically disordered proteins (IDPs) do not have a well-defined folded structure but instead behave as extended polymer chains in solution. Many IDPs are rich in glycine residues, which create steric barriers to secondary structuring and protein folding. Inspired by this feature, we have studied how the introduction of glycine residues influences the secondary structure of a model polypeptide, poly(l-glutamic acid), a helical polymer.

Group-Transfer Polymerization-Induced Self-Assembly (GTPISA) in Non-polar Media: An Organocatalyzed Route to Block Copolymer Nanoparticles at Room Temperature.

Polymerization-induced self-assembly (PISA) enables the synthesis at large scale of a wide variety of functional nanoparticles. However, a large number of works are related to controlled radical polymerization (CRP) methods and are generally undertaken at elevated temperatures (>50 °C). Here is the first report on methacrylate-based nanoparticles fabricated by group transfer polymerization-induced self-assembly (GTPISA) in non-polar media (n-heptane).

Controlling polymersome size through microfluidic-assisted self-assembly: Enabling 'ready to use' formulations for biological applications.

The self-assembly of poly(ethylene glycol)-block-poly(trimethylene carbonate) PEG-b-PTMC copolymers into vesicles, also referred as polymersomes, was evaluated by solvent displacement using microfluidic systems. Two microfluidic chips with different flow regimes (micromixer and Herringbone) were used and the impact of process conditions on vesicle formation was evaluated. As polymersomes are sensitive to osmotic variations, their preparation under conditions allowing their direct use in biological medium is of major importance.

Control of Enzyme Reactivity in Response to Osmotic Pressure Modulation Mimicking Dynamic Assembly of Intracellular Organelles.

In response to variations in osmotic stress, in particular to hypertonicity associated with biological dysregulations, cells have developed complex mechanisms to release their excess water, thus avoiding their bursting and death. When water is expelled, cells shrink and concentrate their internal bio(macro)molecular content, inducing the formation of membraneless organelles following a liquid-liquid phase separation (LLPS) mechanism. To mimic this intrinsic property of cells, functional thermo-responsive elastin-like polypeptide (ELP) biomacromolecular conjugates are herein encapsulated into self-assembled lipid vesicles using a microfluidic system, together with polyethylene glycol (PEG) to mimic cells' interior crowded microenvironment.

Light-Responsive Elastin-Like Peptide-Based Targeted Nanoparticles for Enhanced Spheroid Penetration.

We describe here a near infrared light-responsive elastin-like peptide (ELP)-based targeted nanoparticle (NP) that can rapidly switch its size from 120 to 25 nm upon photo-irradiation. Interestingly, the targeting function, which is crucial for effective cargo delivery, is preserved after transformation. The NPs are assembled from (targeted) diblock ELP micelles encapsulating photosensitizer TT1-monoblock ELP conjugates.

Improving aqueous solubility of paclitaxel with polysarcosine-b-poly(γ-benzyl glutamate) nanoparticles.

New stealth amphiphilic copolymers based on polysarcosine (PSar) rather than poly(ethylene glycol) (PEG) have gained more attention for their use as excipients in nanomedicine. In this study, several polysarcosine-b-poly(γ-benzyl glutamate) (PSar-b-PGluOBn) block copolymers were synthesized by ring opening polymerization (ROP) of the respective N-carboxyanhydrides (NCAs) and were characterized by Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (H NMR) and size-exclusion chromatography (SEC). Copolymers had different PGluOBn block configuration (racemic L/D, pure L or pure D), degrees of polymerization of PSar between 28 and 76 and PGluOBn between 9 and 93, molar masses (M) between 5.

Emerging opportunities in bioconjugates of Elastin-like polypeptides with synthetic or natural polymers.

Nature is an everlasting source of inspiration for chemical and polymer scientists seeking to develop ever more innovative materials with greater performances. Natural structural proteins are particularly scrutinized to design biomimetic materials. Often characterized by repeat peptide sequences, that together interact by inter- and intramolecular interactions and form a 3D skeleton, they contribute to the mechanical properties of individual cells, tissues, organs, and whole organisms.

Efficient Gene Delivery of Tailored Amphiphilic Polypeptides by Polyplex Surfing.

Within this study, an amphiphilic and potentially biodegradable polypeptide library based on poly[(4-aminobutyl)-l-glutamine--hexyl-l-glutamine] [P(AB-l-Gln--Hex-l-Gln)] was investigated for gene delivery. The influence of varying proportions of aliphatic and cationic side chains affecting the physicochemical properties of the polypeptides on transfection efficiency was investigated. A composition of 40 mol% Hex-l-Gln and 60 mol % AB-l-Gln () was identified as best performer over polypeptides with higher proportions of protonatable monomers.

Mannose-based surfactant as biofunctional nanoemulsion stabilizer.

The development and implementation of new amphiphiles based on natural resources rather than petrochemical precursors is an essential requirement due to their feedstock depletion and adverse environmental impacts. In addition, the use of bio-based surfactants can provide unique characteristics and improve the properties and versatility of the colloidal systems in which they are applied, such as emulsions. Here, the emulsification properties of a synthesized biocompatible mannose-based surfactant were investigated.

Aqueous synthesis and self-assembly of bioactive and thermo-responsive HA--ELP bioconjugates.

The design of synthetic (bio)macromolecules that combine biocompatibility, self-assembly and bioactivity properties at the molecular level is an intense field of research for biomedical applications such as (nano)medicine. In this contribution, we have designed and synthesized a library of bioactive and thermo-responsive bioconjugates from elastin-like polypeptides (ELPs) and hyaluronic acid (HA) in order to access bioactive self-assembled nanoparticles. These were prepared by a simple synthetic and purification strategy, compatible with the requirements for biological applications and industrial scale-up.

Memory Effect in Thermoresponsive Proline-based Polymers.

We report that synthetic polymers consisting of L-proline monomer units exhibit temperature-driven aggregation in water with unprecedented hysteresis. This protein-like behavior is robust and governed by the chirality of the proline units. It paves the way to new processes, driven by either temperature or ionic strength changes, such as a simple "with memory" thermometer.

The quantum dot organic dye conundrum for ratiometric FRET-based biosensors: which one would you chose?

Förster resonance energy transfer (FRET) is a widely used and ideal transduction modality for fluorescent based biosensors as it offers high signal to noise with a visibly detectable signal. While intense efforts are ongoing to improve the limit of detection and dynamic range of biosensors based on biomolecule optimization, the selection of and relative location of the dye remains understudied. Herein, we describe a combined experimental and computational study to systematically compare the nature of the dye, , organic fluorophore (Cy5 or Texas Red) inorganic nanoparticle (QD), and the position of the FRET donor or acceptor on the biomolecular components.

Assembly of Fluorescent Polymer Nanoparticles Using Different Microfluidic Mixers.

Nanoprecipitation is a facile and efficient approach to the assembly of loaded polymer nanoparticles (NPs) for applications in bioimaging and targeted drug delivery. Their successful use in clinics requires reproducible and scalable synthesis, for which microfluidics appears as an attractive technique. However, in the case of nanoprecipitation, particle formation depends strongly on mixing.

Design and Self-Assembly of Sugar-Based Amphiphiles: Spherical to Cylindrical Micelles.

Sugar-based amphiphiles are a relevant natural alternative to synthetic ones due to their biodegradable properties. An understanding of their structure-assembly relationship is needed to allow the concrete synthesis of suitable derivatives. Here, four different mannose-derivative surfactants are characterized by pendant drop, dynamic light scattering, small-angle X-ray scattering, cryotransmission electron microscopy, and molecular dynamics techniques in aqueous media.

Tear of lipid membranes by nanoparticles.

Health concerns associated with the advent of nanotechnologies have risen sharply when it was found that particles of nanoscopic dimensions reach the cell lumina. Plasma and organelle lipid membranes, which are exposed to both the incoming and the engulfed nanoparticles, are the primary targets of possible disruptions. However, reported adhesion, invagination and embedment of nanoparticles (NPs) do not compromise the membrane integrity, precluding direct bilayer damage as a mechanism for toxicity.