Biomechanics of the progression of colorectal carcinomas
Giulia Fornabaio, Synthetic morphogenesis
According to the World Health Organization, cancer is one of the main causes of death worldwide, with colorectal carcinoma (CRC) being the second-leading cause of tumour related-death. The high rate of mortality of CRCs is principally attributed to the metastasis of neoplastic cells from the primary tumour to secondary organs such as the liver, the lung and the peritoneum. These cells can disseminate either as single isolated cells or as collective clusters, undergoing a series of molecular and cellular changes commonly known as Epithelial to Mesenchymal Transition (EMT). However, in 2018, Jaulin and her team described a novel modality of peritoneal metastatic spread characterized by the presence of large clusters of cancer cells, which maintain their epithelial properties and display an outward apical polarity. These clusters of cells, termed tumour spheres with inverted polarity (TSIPs), were found in peritoneal effusions of CRCs patients showing early KRAS mutation and hypermethylation of CpG Islands.
TSIPs originate through a series of morphological changes: the first event is the sprouting of hypermethylated epithelia, followed by their apical budding, leading to the formation of rounded spherical clusters of cells called buds, and the subsequent cleavage of the newly formed spheres. How cell and tissue mechanics drive this process is still unclear. To provide novel insights into this metastatic cascade, our project aims at deciphering the biomechanical and cellular events regulating the formation of buds in colorectal cancer cell lines. Employing a combination between cellular biology techniques with biophysical methods, we showed that this process is characterized by over-proliferation and local changes in cell adhesion, coupled with the formation of cellular vortexes surrounding the buds. Our study demonstrates that buds development in colorectal carcinomas epithelia is governed by morphological transitions occurring entirely at multicellular level, rather than by single cells aggregation or cell extrusion.
Imaging Functional Organic Bioelectronic Platforms at the Nanoscale
, Nanoscale Bioelectrical Characterization
In recent years, many organic bioelectronic platforms have emerged to bridge the signaling gap between biology and technology. Organic bioelectronic platforms based on transistor architecture, commonly known as Electrolyte-Gated Transistors (EGTs), are an excellent tool to selectively sense, record, and monitor biological signals and states, and convert them into measurable electrical signals.1 Biological events happening at the nanoscale are now routinely studied and characterized by a millimeter-sized transistor. However, it is not well understood how these nanoscale events interact with the transistor’s nanoscale properties leading to a change in their macroscale response. This gap in understanding is purely due to the lack of techniques to image the electrical properties in a liquid environment. Towards this goal, our group has adapted in-Liquid Scanning Dielectric Microscopy to unravel the inner working of EGTs at the nanoscale.2 Besides apparent topographical changes, electrical properties, like conductivity and interfacial capacitance, and mechanical properties are mapped at the nanoscale in a working transistor in liquid. The vast information extracted has made it possible to correlate the nanoscale processes with the macroscale response, offering improved understanding and the potential for substantial optimization of bioelectronic devices.
This PhD Discussion session will be held at Tower I, 11th floor Baobab room, there will be 30 avialable seats, the free spots will be assigned on a first come first served basis.