Pascucci, A. | bioRxiv Science

bioRxiv2026

Viscoelasticity drives EMT in pancreatic intraepithelial neoplasia

Pancreatic intraepithelial neoplasia (PanIN) is a precursor of pancreatic adenocarcinoma (PDAC) and therefore critical to understand for identifying early-stage diagnostic and therapeutic targets. During PanIN, epithelial-to-mesenchymal transition (EMT) of pancreatic epithelial cancer cells is a crucial event which promotes invasion and early dissemination of cells into circulation before the full development of PDAC tumours. Changes in tissue mechanics are apparent during progression from PanIN to PDAC and increased local and global elasticity has been mathematically modelled in PanIN tissue as a predictive tool for diagnostics and development of personalized therapies. Aside from elasticity, viscoelasticity is emerging as a key feature of cancer which affects tissue mechanics through a combination of elastic and viscous components. Viscoelasticity has recently been shown to drive mechanosensitive cell behaviour and is known to change dramatically in PDAC progression. Hydrogels, as water-swollen polymer networks, are effective extracellular matrix (ECM) models that can recapitulate the viscoelastic properties of natural tissue. Despite this, hydrogels developed for studying cell behaviour in PanIN use purely elastic materials or have neglected the viscous component. Here, using PDAC mouse models, we show that viscoelasticity dynamically alters between healthy and PanIN-bearing tissue and have decoupled the role of elasticity and viscosity during EMT of pancreatic epithelial cancer cells using two-dimensional (2D) polyacrylamide (PAAm) hydrogels. Our work shows viscosity is critical in driving phenotypic changes associated with EMT in a pancreatic epithelial cancer cell line. These findings identify viscosity as an integral component of cell mechanosensing as PanIN develops, which may contribute to initial metastatic events via dissemination from the developing primary tumour. This should be explored further to potentially reveal novel diagnostic and therapeutic targets.

cancer biology↗

bioRxiv2025

Aberrant cerebrovascular reactivity presents as an early biomarker of psychosis susceptibility in patients with 22q11.2DS

The brains ability to regulate blood flow is fundamental to both its function and development. In the context of neurodevelopmental disorders such as schizophrenia, understanding the complex interactions between cerebrovascular health and brain function is crucial for unraveling the pathophysiology of psychosis. This study investigates the developmental trajectory of cerebrovascular reactivity (CVR) in 22q11 deletion syndrome (22q11.2DS) compared to healthy controls, and its association with psychosis susceptibility. Using a longitudinal data-set of resting-state fMRI, we mapped voxel-level CVR across development. We found significant and early CVR impairments in 22q11.2DS, and in particular in those who later developed positive psychotic symptoms (PPS+). These impairments were evident within the anterior cingulate cortex, frontal lobes, and globi pallidi (GB). We propose that the pattern of CVR reduction presenting early during childhood is possibly linked to blood brain barrier impairment. A decrease in CVR during childhood and within the frontal regions and GB was predictive of subsequent development of positive psychotic symptoms (PPS), which often occurs during adolescence in 22q11.2DS patients. These findings suggest that cerebrovascular health is critical for normal brain development, particularly in regions like the striatum, which are vulnerable to vascular damage due to their anatomical features. These results underline the potential of CVR as an early biomarker for psychosis vulnerability, emphasizing the need for targeted interventions to mitigate neurodevelopmental disruptions of cerebrovascular health in 22q11.2DS.

neuroscience↗