PhD Discussion: Aina Albajar and Ainhoa Gonzalez
Studying the mechanical regulation of nucleocytoplasmic transport using Single Molecule Tracking
Aina Albajar-Sigalé, Cellular and Molecular Mechanobiology Group
Cellular function relies on the precise regulation of macromolecular transport between the cytoplasm and the nucleus, a process governed by Nuclear Pore Complexes (NPCs). While traditional understanding held that transport through NPCs was mainly dictated by the physicochemical properties of the transported molecules, recent research has revealed an additional layer of regulation driven by mechanical forces. Whether applied directly or transmitted through the cytoskeleton, mechanical signals have the capacity to deform the nucleus and, consequently, alter the conformation of NPCs, increasing their diameter. This changes nucleocytoplasmic transport rates and impacts the localisation of a variety of signalling molecules. However, the cellular components responsible for force transmission to NPCs as well as the spatial distribution of this effect throughout the nuclear envelope, remain poorly understood. Here, we aim to answer these questions by investigating whether isolated nuclei, a minimal system depleted of all the cell’s cytoplasmic machinery, still exhibit mechanosensitive nucleocytoplasmic transport. To do so, we apply mechanical force by confining isolated nuclei to a certain micrometre height and, simultaneously, measure nucleocytoplasmic transport rates by tracking individual dextran molecules translocating through NPCs. Our results show that molecules translocate faster in confined nuclei, suggesting that unspecific force application to a passive nuclear envelope is enough to induce conformational changes in NPCs and alter transport dynamics.
Laser-Induced Vapor Nanobubbles Trigger Immunogenic Cell Death Prophylactic Immunity in Bladder Cancer Models
Ainhoa G. Caelles, Smart Nano-Bio-Devices Group
Bladder cancer (BC) is the 10th most common malignancy worldwide, and despite treatments such as intravesical chemotherapy and Bacille Calmette-Guérin (BCG) immunotherapy, high relapse rates persist, especially in non-muscular invasive BC (NMIBC). Photothermal therapy (PTT) emerges as a promising non-invasive approach inducing tumor ablation while promoting immunogenic cell death (ICD). This project studies iron oxide nanoparticles (IONPs) as photosensitizers for laser-induced vapor nanobubbles (VNBs) in MB49 cells and its potential to induce cell death and prevent tumor relapse in subcutaneous/orthotopic murine models.
