Prof Sonia Antoranz Contera

Abstract:

The last five decades of molecular and systems biology research have provided unprecedented insights into the molecular and genetic basis of many cellular processes. Despite these insights, however, it is arguable that there is still only limited predictive understanding of cell behaviours. In particular, the basis of heterogeneity in single-cell behaviour and the initiation of many different metabolic, transcriptional or mechanical responses to environmental stimuli remain largely unexplained. To go beyond the status quo, the understanding of cell behaviours emerging from molecular genetics must be complemented with physical and physiological ones, focusing on the intracellular and extracellular conditions within and around cells. Here, we argue that such a combination of genetics, physics and physiology can be grounded on a bioelectrical conceptualization of cells. We motivate the reasoning behind such a proposal and describe examples where a bioelectrical view has been shown to, or can, provide predictive biological understanding. In addition, we discuss how this view opens up novel ways to control cell behaviours by electrical and electrochemical means, setting the stage for the emergence of bioelectrical engineering.

Abstract:

Intercalation of drug molecules into synthetic DNA nanostructures formed through self-assembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programmability including facile drug release into or near to target cells. Such favourable properties may enable high initial loading and efficient release for a predictable number of drug molecules per nanostructure carrier, important for efficient delivery of safe and effective drug doses to minimise non-specific release away from target cells. However, basic questions remain as to how intercalation-mediated loading depends on the DNA carrier structure. Here we use the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D DNA origami tile as a simple model system to investigate intercalation-mediated loading. We employed multiple biophysical techniques including single-molecule fluorescence microscopy, atomic force microscopy, gel electrophoresis and controllable damage using low temperature plasma on synthetic DNA origami samples. Our results indicate that not all potential DNA binding sites are accessible for dye intercalation, which has implications for future DNA nanostructures designed for targeted drug delivery.

Abstract:

Polymeric magnetic spherical microparticles are employed as sensors/actuators in lab-on-a-chip applications, small-scale robotics and biomedical/biophysical assays. Achieving controlled stable motion of the microparticles in a fluid environment using low intensity magnetic fields is necessary to achieve much of their technological potential; this requires that the microparticle is magnetically anisotropic, which is difficult to achieve in spheres. Here we have developed a simple method to synthesise anisotropic ellipsoidal microparticles (average eccentricity 0.60 ± 0.14) by applying a magnetic field during synthesis, using a nanocomposite of polycaprolactone (PCL) with Fe3O4 nanowires. The “microellipsoids” are thoroughly characterised using optical microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). Their suitability for magnetically controlled motion is demonstrated by analysing their rotation in low magnetic fields (0.1, 1, 5, 10 and 20 mT) at varying rotational frequencies (1 Hz and 5 Hz). The microellipsoids are able to follow smoothly and continuously the magnetic field, while commercial spherical particles fail to continuously follow the magnetic field, and oscillate backwards and forwards resulting in much lower average angular speeds. Furthermore, only 23 % of commercial particles analysed rotated at 1 Hz and 26 % at 5 Hz, whereas 77 % of our ellipsoidal particles rotated at 1 Hz, and 74 % did at 5 Hz.