Biocompatibility | EPFL Graph Search

Biocompatibility is related to the behavior of biomaterials in various contexts. The term refers to the ability of a material to perform with an appropriate host response in a specific situation. The ambiguity of the term reflects the ongoing development of insights into how biomaterials interact with the human body and eventually how those interactions determine the clinical success of a medical device (such as pacemaker, hip replacement or stent). Modern medical devices and prostheses are often made of more than one material so it might not always be sufficient to talk about the biocompatibility of a specific material. Even the same materials, such as diamond-like carbon coatings, may show different levels of biocompatibility based on the manufacturing conditions and characteristics. Since the immune response and repair functions in the body are so complicated it is not adequate to describe the biocompatibility of a single material in relation to a single cell type or tissue. So

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

A Biocompatible in Vivo Ligation Reaction and Its Application for Noninvasive Bioluminescent Imaging of Protease Activity in Living Mice

Ke Cheng, Aurélien Godinat, Douglas Hanahan, Gennady Nikitin

The discovery of biocompatible reactions had a tremendous impact on chemical biology, allowing the study of numerous biological processes directly in complex systems. However, despite the fact that multiple biocompatible reactions have been developed in the past decade, very few work well in living mice. Here we report that D-cysteine and 2-cyanobenzothiazoles can selectively react with each other in vivo to generate a luciferin, substrate for firefly luciferase. The success of this "split luciferin" ligation reaction has important implications for both in vivo imaging and biocompatible labeling strategies. First, the production of a luciferin substrate can be visualized in a live mouse by bioluminescence imaging (BLI) and furthermore allows interrogation of targeted tissues using a "caged" luciferin approach. We therefore applied this reaction to the real-time noninvasive imaging of apoptosis associated with caspase 3/7. Caspase-dependent release of free D-cysteine from the caspase 3/7 peptide substrate Asp-Glu-Val-Asp-D-Cys (DEVD-(D-Cys)) allowed selective reaction with 6-amino-2-cyanobenzothiazole (NH2-CBT) in vivo to form 6-amino-D-luciferin with subsequent light emission from luciferase. Importantly, this strategy was found to be superior to the commercially available DEVD-aminoluciferin substrate for imaging of caspase 3/7 activity. Moreover, the split luciferin approach enables the modular construction of bioluminogenic sensors, where either or both reaction partners could be caged to report on multiple biological events. Lastly, the luciferin ligation reaction is 3 orders of magnitude faster than Staudinger ligation, suggesting further applications for both bioluminescence and specific molecular targeting in vivo.

Amer Chemical Soc2013

A biocompatible "split luciferin" reaction and its application for non-invasive bioluminescent imaging of protease activity in living animals

Ghyslain Martial Alain Budin, Aurélien Godinat, Alma Rosa Morales Morales

The great complexity of many human pathologies, such as cancer, diabetes, and neurodegenerative diseases, requires new tools for studies of biological processes on the whole organism level. The discovery of novel biocompatible reactions has tremendously advanced our understanding of basic biology; however, no efficient tools exist for real-time non-invasive imaging of many human proteases that play very important roles in multiple human disorders. We recently reported that the "split luciferin" biocompatible reaction represents a valuable tool for evaluation of protease activity directly in living animals using bioluminescence imaging (BLI). Since BLI is the most sensitive in vivo imaging modality known to date, this method can be widely applied for the evaluation of the activity of multiple proteases, as well as identification of their new peptide-specific substrates. In this unit, we describe several applications of this "split luciferin" reaction for quantification of protease activities in test tube assays and living animals.

2014

Supramolecular structures of polypeptides

Daniela Silvano

EPFL2008