Competitive Registration Fields for The Development of Complex Block Copolymer Structures by A Layer-by-Layer Approach.

Block copolymer (BCP) self-assembly in thin films is an elegant method to generate nanometric features with tunable geometrical configurations. By combining directed assembly and hybridization methods, advances in nano-manufacturing have been attested over the past decades with flagship applications in lithography and optics. Nevertheless, the range of geometrical configurations is limited by the accessible morphologies inherent to the energy minimization process involved in BCP self-assembly. Layering of nanostructured BCP thin films has been recently proposed in order to enrich the span of nanostructures derived from BCP self-assembly with the formation of non-native heterostructures such as double-layered arrays of nanowires or dots-on-line and dots-in-hole hierarchical structures. In this work, the layer-by-layer method is further exploited for the generation of nano-mesh arrays using nanostructured BCP thin films. In particular, a subtle combination of chemical and topographical fields is leveraged in order to demonstrate design rules for the controlled registration of a BCP layer on top of an underneath immobilized one by the precise tuning of the interfacial chemical field between the two BCP layers.

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. Its behavior was evaluated in the presence of four different natural oils (castor, sunflower, olive and soybean) as well as two different aqueous phases (pure water and phosphate-buffered saline). The results highlighted its interest as surfactant in O/W nanoemulsions for all tested oil and aqueous phases, using a low-energy preparation protocol and relatively low surfactant concentrations. Furthermore, the mannose groups present on the polar head of the surfactant and adsorbed on the surface of the emulsion droplets were shown to retain their native biological properties. The specific mannose-concanavalin A binding was observed in vitro by the designed nanoemulsions, revealing the biorecognition properties of the surfactant and its potential applicability as a nanocarrier.

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. Measurements denote how the polysaccharide average degree of polymerization (DP¯) and the addition of a hydroxyl group to the hydrophobic tail, and thus the presence of a second hydrophilic moiety, affect their self-assembly. A variation in the DP¯ of the amphiphile has no effect in the critical micelle concentration in contrast to a change in the hydrophobic molecular region. Moreover, high-DP¯ amphiphiles self-assemble into spherical micelles irrespective of the hydroxyl group presence. Low-DP¯ amphiphiles with only one hydrophilic moiety form cylindrical micelles, while the addition of a hydroxyl group to the tail leads to a spherical shape.

Amphiphilic polymers for aggregation-induced emission at air/liquid interfaces.

Polymersomes and related self-assembled nanostructures displaying Aggregation-Induced Emission (AIE) are highly relevant for plenty of applications in imaging, biology and functional devices. Experimentally simple, scalable and universal strategies for on-demand self-assembly of polymers rendering well-defined nanostructures are highly desirable. A purposefully designed combination of amphiphilic block copolymers including tunable lengths of hydrophilic polyethylene glycol (PEGm) and hydrophobic AIE polymer poly(tetraphenylethylene-trimethylenecarbonate) (P(TPE-TMC)n) has been studied at the air/liquid interface. The unique 2D assembly properties have been analyzed by thermodynamic measurements, UV-vis reflection spectroscopy and photoluminescence in combination with molecular dynamics simulations. The (PEG)m-b-P(TPE-TMC)n monolayers formed tunable 2D nanostructures self-assembled on demand by adjusting the available surface area. Tuning of the PEG length allows to modification of the area per polymer molecule at the air/liquid interface. Molecular detail on the arrangement of the polymer molecules and relevant molecular interactions has been convincingly described. AIE fluorescence at the air/liquid interface has been successfully achieved by the (PEG)m-b-P(TPE-TMC)n nanostructures. An experimentally simple 2D to 3D transition allowed to obtain 3D polymersomes in solution. This work suggests that engineered amphiphilic polymers for AIE may be suitable for selective 2D and 3D self-assembly for imaging and technological applications.

Folding and self-assembly of short intrinsically disordered peptides and protein regions.

Proteins and peptide fragments are highly relevant building blocks in self-assembly for nanostructures with plenty of applications. Intrinsically disordered proteins (IDPs) and protein regions (IDRs) are defined by the absence of a well-defined secondary structure, yet IDPs/IDRs show a significant biological activity. Experimental techniques and computational modelling procedures for the characterization of IDPs/IDRs are discussed. Directed self-assembly of IDPs/IDRs allows reaching a large variety of nanostructures. Hybrid materials based on the derivatives of IDPs/IDRs show a promising performance as alternative biocides and nanodrugs. Cell mimicking, in vivo compartmentalization, and bone regeneration are demonstrated for IDPs/IDRs in biotechnological applications. The exciting possibilities of IDPs/IDRs in nanotechnology with relevant biological applications are shown.

Optimization of Amino Acid Sequence of Fmoc-Dipeptides for Interaction with Lipid Membranes.

Fmoc-dipeptides appear as highly relevant building blocks in smart hydrogels and nanovehicles for biological applications. The interactions of the Fmoc-dipeptides with the cell membrane determine the efficiency of the nanomaterials based on the Fmoc-dipeptides' internalization of nanovehicles for drug delivery. Here, we aim to understand the interplay of the interactions between the Fmoc-dipeptides and a phospholipid surface as a function of the amino acid sequence. The DMPA (1,2-dimyristoyl- sn-glycero-3-phosphate) phospholipid in Langmuir monolayers was used as a model cell surface. A set of seven derivatives of Fmoc-dipeptides with a broad range of hydrophobicity were included. Mixed monolayers composed of DMPA/Fmoc-dipeptides in an equimolar ratio were built and characterized in situ at the air/water interface. Surface pressure-molecular area isotherms (π- A), Brewster angle microscopy (BAM), and UV-vis reflection spectroscopy (Δ R) were combined to provide a holistic picture of the interactions of the Fmoc-dipeptide with the phospholipid molecules. An increase in the hydrophobicity led to enhanced interaction of the Fmoc-dipeptide and DMPA molecules. The compression of the mixed monolayer could displace a significant fraction of the Fmoc-dipeptide from the monolayer. High hydrophobicity promoted self-assembly of the Fmoc-dipeptides over interaction with the phospholipid surface. The interplay of these two phenomena was analyzed as a function of the amino acid sequence of the Fmoc-dipeptides. The toxicity effect of Fmoc-FF could be observed and detailed at the molecular level. This study suggests that the adjustment of the hydrophobicity of the Fmoc-dipeptides within a defined range might optimize their efficiency for interaction with the lipid membranes. A semiquantitative guide for the chemical design of Fmoc-dipeptides for biological applications is proposed herein.

Subtle chemical modification for enrichment of Fmoc-amino acid at a phospholipid interface.

Amino acids including the Fmoc group (9-fluorenylmethyloxycarbonyl) are bioinspired molecules that display intriguing features in self-assembly and biological applications. The influence of a delicate chemical modification between Fmoc-F and Fmoc-Y on the interaction with a phospholipid surface was analyzed. Langmuir monolayers of the 1,2-dimyristoyl-sn-glycero-3-phosphate (DMPA) phospholipid were used to mimic the eukaryotic cell membrane. In situ Brewster angle microscopy and UV-vis reflection spectroscopy provided insights on the effect of the Fmoc-amino acid derivatives on the DMPA phospholipid. The formation of H-bonds between the Fmoc-Y and the DMPA molecules was assessed, demonstrating the crucial role of the hydroxyl group of Fmoc-Y in enhancing the interaction with biosurfaces.

Fluorinated CdSe/ZnS quantum dots: Interactions with cell membrane.

Fluorescent inorganic quantum dots are highly promising for biomedical applications as sensing and imaging agents. However, the low internalization of the quantum dots, as well as for most of the nanoparticles, by living cells is a critical issue which should be solved for success in translational research. In order to increase the internalization rate of inorganic CdSe/ZnS quantum dots, they were functionalized with a fluorinated organic ligand. The fluorinated quantum dots displayed an enhanced surface activity, leading to a significant cell uptake as demonstrated by in vitro experiments with HeLa cells. We combined the experimental and computational results of Langmuir monolayers of the DPPC phospholipid as a model cell membrane with in vitro experiments for analyzing the mechanism of internalization of the fluorinated CdSe/ZnS quantum dots. Surface pressure-molecular area isotherms suggested that the physical state of the DPPC molecules was greatly affected by the quantum dots. UV-vis reflection spectroscopy and Brewster Angle Microscopy as in situ experimental techniques further confirmed the significant surface concentration of quantum dots. The disruption of the ordering of the DPPC molecules was assessed. Computer simulations offered detailed insights in the interaction between the quantum dots and the phospholipid, pointing to a significant modification of the physical state of the hydrophobic region of the phospholipid molecules. This phenomenon appeared as the most relevant step in the internalization mechanism of the fluorinated quantum dots by cells. Thus, this work sheds light on the role of fluorine on the surface of inorganic nanoparticles for enhancing their cellular uptake.

Surface-Active Fluorinated Quantum Dots for Enhanced Cellular Uptake.

Fluorescent nanoparticles, such as quantum dots, hold great potential for biomedical applications, mainly sensing and bioimaging. However, the inefficient cell uptake of some nanoparticles hampers their application in clinical practice. Here, the effect of the modification of the quantum dot surface with fluorinated ligands to increase their surface activity and, thus, enhance their cellular uptake was explored.

Unravelling the 2D self-assembly of Fmoc-dipeptides at fluid interfaces.

Dipeptides self-assemble into supramolecular structures showing plenty of applications in the nanotechnology and biomedical fields. A set of Fmoc-dipeptides with different aminoacid sequences has been synthesized and their self-assembly at fluid interfaces has been assessed. The relevant molecular parameters for achieving an efficient 2D self-assembly process have been established. The self-assembled nanostructures of Fmoc-dipeptides displayed significant chirality and retained the chemical functionality of the aminoacids. The impact of the sequence on the final supramolecular structure has been evaluated in detail using in situ characterization techniques at air/water interfaces. This study provides a general route for the 2D self-assembly of Fmoc-dipeptides.