APRÈN. Portal de la producció docent del professorat de la UPC

Zebrafish embryos are a highly valuable model system for drug discovery due to their con- served vertebrate neural circuits. Studying coiling behavior in 1-day-old embryos offers a means to identify compounds that impact motor function. However, existing software lacks the capability to track body axis changes during coiling. Here, we present ZMAT01 and ZMAT02, analytical toolkits based on DeepLabCut technology. ZMAT quantifies both the frequency and body axis variations during coiling behavior, enabling a more precise analysis compared to traditional methods. This enhanced precision has the potential to revolutionize drug discovery efforts by facilitating the identification of compounds targeting specific motor functions.

Cell culture in vitro plays a crucial role in understanding cellular interactions, tissue morphology, protein production, and drug mechanisms. However, traditional 2D cell cultures have limitations in mimicking the complex 3D environment of tumours, impacting their physiological relevance. This thesis explores the development of 3D hydrogel microspheres using alginate, specifically tailored to simulate the lung cancer microenvironment. These microspheres, ranging from 20 µm to 60 µm in size, were synthesized via an emulsion technique and surface-modified using a Layer-by-Layer (LbL) approach to graft collagen, hyaluronic acid, and heparan sulphate?key extracellular matrix molecules found in lung tumours. Characterization via Fourier Transform Infrared Spectroscopy (FTIR), Thermal Gravimetric Analysis (TGA), and biochemical assays confirmed successful functionalization. Preliminary cell culture experiments using A549 lung carcinoma epithelial cells demonstrated promising cell adhesion, proliferation, and interaction dynamics within the 3D microenvironment provided by the hydrogel microspheres. This study highlights the potential of alginate-based microgel as an effective platform for studying lung cancer biology in vitro. Future directions include expanding the model to incorporate additional cell types and extracellular factors to enhance its biomimetic properties for broader applications in cancer research and drug development.

Polycyclic aromatic hydrocarbons (PAHs) constitute a class of carbon and hydrogen compounds characterized by the presence of two or more benzene rings, either individually or fused together within their molecular structure. These compounds, known for their limited solubility in water, can undergo photo-oxidation and degradation to simpler substances. In this study, we focused on anthracene (C$_{14}$H$_{10}$), a typical PAH, given its significance in pharmaceutical applications. We investigated the molecular ordering (positional and orientational) of water molecules around anthracene using molecular dynamics (MD) simulations and neutron diffraction experiments. The relevant of this work ascertain what role the water plays in the solubility in anthracene and can guide future investigations of drug solubility in polycyclic aromatic hydrocarbons.

This study explores gas sorption in polymer matrices using a molecular dynamics (MD) simulation framework and the Widom test insertion method. The simulations focused on \(\mathrm{CO_2}\), \(\mathrm{N_2}\), and Ar to compute Henry's law constants, comparing results with experimental data. Additionally, the polymer matrix was successfully described in terms of its structural and chemical properties, providing a comprehensive basis for sorption studies. The calculated \(\langle H \rangle\) for \(\mathrm{CO_2}\) (738.5002 MPa) showed a significant deviation from experimental values, indicative of current methodological limitations. \(\mathrm{N_2}\) and Ar simulations yielded \(\langle H \rangle\) values of 109.924 MPa and 165.2136 MPa, respectively, lower than experimental benchmarks. Refinements in simulation parameters and methodologies are crucial for improving predictive accuracy. Future research will expand to include more gases and diverse polymers, and enhance computational efficiency.

This study investigates the volume phase transition (VPT) behavior of thermosensitive hydrogels, specifically focusing on Poly(N-isopropylacrylamide) (PNiPA) and Poly(N-n-propylmethacrylamide) (PNnPMA) polymer hydrogels. Thermosensitive hydrogels are networks that can absorb water and are responsive to temperature. It has reversible volume changes governed by the volume phase transition temperature (VPTT). The study aims to study the VPTT of PNiPA and PNnPMA hydrogels using molecular dynamics (MD) simulations. These simulations provide insights into the polymers' structural and dynamic behavior below and above their VPTT. The results highlight the differences in VPTT between the two hydrogels due to their molecular structure differences. Key findings show that PNiPA, with its hydrophilic isopropyl group, exhibits a higher VPTT due to stronger water-polymer interactions requiring more energy for dehydration. In contrast, the more hydrophobic PNnPMA shows a lower VPTT. Analyses of root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), hydrogen bonding (HB), radial distribution functions (RDFs), and coordination numbers (CNs) provide a comprehensive understanding of the polymers' behavior at different temperatures.

Electrochemical sensors have shown significant promise in advancing point-of-care diagnostics, as exemplified by commercialization of glucometers. Majority of these sensors are label-free and modulate the electrical properties at their surface when bound to a target analyte. When such sensors are utilized in biofluids, the target recognition and corresponding signal transduction is significantly impacted by the ionic screening at the surface. This ionic screening, termed as Debye length limitation, loaclize the sensitive detection region such that the electrode can transduce only those binding events that happen within a distance of 1 nm from the surface. To this end, we investigated an aptamer-modified thin film sensor as a potential label-free biosensing platform that can combat Debye length limitation. Aptamers are nucleotide sequences, that due to their small size (3-5 nm) can undergo binding-induced conformational changes in close proximity to the sensor surface. This project offers preliminary findings for assembly of these conformation-changing aptamers on a 10 nm thick gold film. The fundamental question we investigated was whether aptamer exposure could reliably and reproducibly alter the resistance of thin films. We obtained promising results which validated the chemistry used for surface modification and showed sensitivity of thin films to aptamer assembly. Since thinner films are anticipated to show improved sensitivity to surface interactions, prospects of etching 10 nm thick films using \ce{KI}/\ce{I_{2}} as an etchant were explored. We obtained promising results which confirmed the possibility of controlled etching of film surface at a rate of few nanometers per minute. These investigations validate the feasibility of a measurement setup capable of achieving both aptamer modification and controlled etching of thin films and hold potential for future applications in small-molecule detection in biofluids.