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PhD Discussion. Margherita Gallano and Carles Prado Morales
Nuclear Envelope Remodelling under Mechanical Perturbation
Margherita Gallano, predoctoral researcher in the Cellular and Molecular Mechanobiology Group
Cells experience mechanical loads during many fundamental processes, including growth, differentiation, and migration. These forces are transmitted to the nucleus and can influence gene expression, ultimately modulating cell behaviour and determining cell fate. The Nuclear Envelope (NE) plays a critical role in this process, as it has been shown to sense cell size variations and activate mechanosensitive signalling pathways. Yet, the phenomenology of NE responses to mechanical stimuli remains largely unexplored. In this project, we aim to characterize the dynamic response of the NE under both stretch and compression, and to unravel the associated mechanosensing mechanisms. To do so, we employ a custom-made microfluidic device to apply controlled stretch to HeLa cells nuclei and a nanoindenter to subject cells to compressive loads. Using single cells and isolated nuclei as model systems, we aim to distinguish active from passive processes of NE remodelling. Our results demonstrate that isolated nuclei undergo NE remodelling upon strain application, characterised by flattening of nuclear envelope wrinkles and increase in nuclear volume. In indentation experiments on intact HeLa cells, we observe rapid NE wrinkling upon release of the compressive load, followed by a gradual restoration of the original nuclear morphology.
Topical enzyme-powered nano-mRNA vaccines
Carles Prado, Smart Nano-Bio-Devices group
The skin constitutes the body’s primary defensive barrier, a function attributed to its complex and highly dense architecture. Beyond its protective role, the skin also represents a promising route for drug delivery and vaccination. Current vaccination strategies primarily rely on injectable administration, which targets tissues with relatively low densities of antigen-presenting cells (APCs). This approach can result in limited efficiency, reduced patient compliance, increased infection risk, and higher healthcare costs. In contrast, skin contains a dense network of resident APCs, making it an attractive target for immunization. However, most topical delivery approaches require physical disruption of the stratum corneum (SC) to overcome the barrier, causing adverse effects and local tissue damage. To address these limitations, we have developed a novel needle-free delivery platform based on enzymatically powered nanomotors capable of actively and non-disruptively penetrating the skin barrier. Through self-propulsion and local modulation of the lipid organization of the SC, these nanomotors enhance transport into the viable epidermis and dermis. Our goal is to employ this technology to topically deliver mRNA to epidermal Langerhans cells and dermal dendritic cells and to evaluate its performance in a human relevant model.
