Liaison chimique | EPFL Graph Search

Une liaison chimique est une interaction durable entre plusieurs atomes, ions ou molécules, à une distance permettant la stabilisation du système et la formation d'un agrégat ou d'une substance chimique. Les électrons, chargés négativement, gravitent autour d’un noyau constitué de protons chargés positivement. Les deux corps s’attirent du fait de la force électrostatique s’exerçant entre les électrons et les protons. Ainsi, un électron positionné entre deux noyaux sera attiré par les deux corps chargés positivement, et les noyaux seront attirés par l’électron. C'est cette attraction qui constitue la liaison chimique. Cette notion comprend une très grande diversité de phénomènes façonnant la matière. Ainsi, la liaison chimique peut être covalente (normale ou de coordination), ionique (issue de l’attraction entre deux ions de charges opposées), métallique, banane, (a)polaire, (dé)localisée, (non) directionnelle, faible, forte, simple, double, triple, σ, π, δ, φ, à un électron, à trois

Mechanical Activation of Chemical Bonds at Polymer Interfaces

Julian Nicolas Bleich

Polymer brushes are a specific class of polymer thin films in which each chain is tethered to the underlying substrate via one chain end. In sufficiently densely grafted assemblies, the individual polymer chains are forced into an extended chain conformation and form a brush-like structure, colloquially referred to as polymer brush. Upon incubation in a good solvent, polymer brushes experience swelling which leads to a tension at the polymer brush - substrate interface. This tension is believed to mechanically facilitate cleaving reactions at the tethering point resulting in the detachment of polymer chains, a process which is known as degrafting. Degrafting, and in the case of crosslinked polymer brushes delamination, has been reported for a large variety of polymer brushes and surface materials. Even though this phenomenon is already known for more than two decades, in depth understanding of the underlying mechanism is lacking and quantitative description of the process is rare. This thesis aims to gain further understanding of the phenomenon by quantitative description of the degrafting process. Further, swelling induced mechanical activation at the tethering point of the polymer to the underlying substrate is discussed in the context of polymer mechanochemistry and presented as a tool to selectively facilitate mechanophore cleavage at the interface. Chapter 1 provides a short historical review on the development of polymer mechanochemistry and gives an overview of commonly applied techniques in the field. The concept of polymer mechanochemistry is then extended to polymer brushes and the discussion results in a number of issues and research questions which are addressed in the subsequent chapters. The preparation and characterization of polymer brushes is not trivial. In Chapter 2 limitations and challenges with focus on experimental reproducibility and thin film characterization are discussed. Chapter 3 discusses the influence of a number of factors, i.e. grafting density and molecular weight of the polymer brush, solvent quality and salt concentration in the incubation medium, on the degrafting process of hydrophilic brushes in aqueous media. Further, the degrafting behavior of polymer brushes prepared from different monomers is compared. It is attempted to correlate degrafting behavior with polymer brush swelling. Contradicting results concerning the actual cleaving point of chains in polymer brushes are found in literature. In Chapter 4 presents structures incorporating only one single potential cleaving point. However, non-specific degrafting could not completely be suppressed. Further, a disulfide bond and oxy-norbornene moiety, commonly used mechanophores, were introduced at the anchoring point. In Chapter 5 the limitation of unwanted background hydrolysis was circumvented by investigating degrafting processes in dry organic media. Specific cleavage of the two mechanophores, disulfide and oxy-norbornene, could be demonstrated.

EPFL2021

Supramolecular structures of polypeptides

Daniela Silvano

The formation of supramolecular structures is a central issue in bio- and nanotechnology and therein plays an important role for many novel developments such as biocompatible materials for integrating living cells or coating for implantable sensing devices as well as for designing smart molecular sensor surfaces for miniaturized bioanalytical techniques. The main focus of this thesis is the investigation of polypeptide layers on surfaces, in particular the formation of self-assembled monolayers (SAMs). SAMs made of long hydrocarbon chains or aromatic molecules comprising surface active and other functional groups have been deeply characterized over decades. Surprisingly, peptide SAMs did not meet the same strong interest despite their great potential in several areas. Natural (20) and artificial amino acids with different physical and chemical properties offer a plethora of novel possibilities to design coating of solid surfaces. In fact their combination in simple oligopeptide sequences provides a huge number of molecular components for the formation of SAMs. Control of SAM features such as density, flexibility, adaptability, interface properties, by tailoring the amino acid sequence opens a new route to manifold applications ranging from fundamental research to nano- and biotechnology. In this thesis different and complementary techniques have been used to investigate the self-assembling ability of polypeptides on surfaces with different physical and chemical properties. Infrared spectroscopy and circular dichroism allowed the determination of the peptide secondary structure on surfaces and in solution. Surface plasmon resonance provided the optical thicknesses of peptide SAMs on gold whereas contact angle measurements have been used to characterize their interfacial properties. In the first part of the thesis, a series of hydrophobic peptides (Ac-Cys-Alax-CONH2, x=3-6) have been self assembled on gold via the thiol group present in the cysteine. The main interest was whether these peptides formed densely packed SAMs with a defined secondary structure within the layer and how the properties of such SAMs depended on the length of the polypeptide backbone. The second part concerns the study of the interactions of an amphipathic helical peptide with various functionalized substrates. The aim was to investigate whether a proper design of the peptide could be used to predetermine its secondary structure on the substrate and whether the orientation of the peptide on the surface could be directly controlled via certain parameters of the surrounding medium. Since the hydrophilic residues of the peptide are histidines, a particular effort was spent in characterizing the peptide adsorption on substrates exposing nitrilotriacetic acid (NTA) moieties. Once established that the adsorption process did not alter its helical structure, the peptide was adsorbed on a substrate exposing two different functional groups: NTA, that could interact with the histidine residues, and methyl groups, that could interact with the hydrophobic ones. The goal was to bind the peptide in different orientation to the same substrate, exploiting the particular spatial distribution of its residues. The third part of this thesis concern the formation of nano- and micro-sized fibrils through molecular self-assembly of simple oligopeptides and protected amino acids. Such systems were chosen as models to investigate the role of the different driving forces in the formation of fibrillar structures. The aromatic protecting group being fixed, it could be shown that the protected amino acids formed fibrils with different sizes and morphologies, or did not form fibrils at all, depending on how strongly their side chains interact. The possibility of forming fibrils by using protected amino acids is of major importance not only in bio-related field but also in organic nanotechnology.

EPFL2008

Engineering Dynamic Hydrogels For In Vitro Organoid Culture

Delphine Lorraine Perle Blondel

Over the past decade, methods to culture stem cells in three dimensions have opened up a plethora of new opportunities for basic and translational research in the life sciences. In particular, the use of natural extracellular matrix (ECM) surrogates, such as mouse tumour-derived Matrigel, unleashed the possibility to recapitulate complex multicellular behaviours in vitro, culminating in the successful derivation of miniaturized organs, termed organoids. While organoids hold tremendous potential as model systems in basic biology, the translational potential of these systems is hampered by their strict dependency on animal-derived matrices that suffer from batch-to-batch variability, potential immunogenicity, and ethical concerns. Recent efforts in engineering covalently crosslinked synthetic hydrogels have attempted to substitute these ill-defined organoid culture systems. However, although these bio-artificial matrices have shown significant potential for 3D organoid culture, their stability and their inherent elastic nature hamper organoid development. Indeed, the native ECM, just like Matrigel, is a highly viscoelastic and dynamic 3D milieu that can relax in response to tissue-induced stress by breaking and subsequently rearranging its network, thus permitting cellular remodelling without compromising the macroscopic stability of the material over time. Therefore, there is a need to develop the next generation of synthetic organoid culture matrices, exhibiting in vivo-like stress-relaxation properties. This thesis provides a perspective on how chemically defined, bio-inspired hydrogels can be designed as potential replacements for native ECM-based matrices for 3D organoid culture. In contrast to traditional synthetic hydrogels that cannot accommodate the dynamic mechanical changes occurring during organoid development, four types of synthetic matrices were developed that are crosslinked, either fully or partially, through dynamic physical bonds. The introduction of such network dynamics is shown to facilitate key morphogenetic processes, such as tissue budding, that are normally absent in purely elastic networks. A unifying hypothesis emerging from these results is that stress relaxation is a crucial requirement for 3D organoid culture. The mechanisms by which stress relaxation influence ISC fate and organoid development remain to be further studied. Preliminary experiments indicated that the stem cells may sense and respond to these characteristics through differential activation of mechanosensing pathways including the transcriptional co-activator YAP. The dynamic hydrogels developed in this thesis hold great promise as tunable environments for stem cell-based self-organization, enabling morphogenetic processes that may be suppressed in conventional synthetic hydrogels systems predominantly used in 3D cell culture applications.

EPFL2019