Amazing work Abby! Congrats to all authors

as usual beautiful data. big congrats!

Holy wow-- this is amazing!! Congratulations!

what a fantastic lineup!!

This work has led us now into a whole range of new projects and collaborations that we are very excited about. This project was a collaboration with the groups of Adam Simonsen at SDU, Cathy Merry and Amanda Wright at Nottingham and Pontus Nordenfelt

This work was inspired and stands on the shoulder of amazing work from several labs that have been developing alginate based hydrogel system and/or have been working on ECM stiffness-mechanotransduction pathways in epithelial structures for decades

Mechanistically, using antibodies, inhibitors etc, Kabilan found that this process of in-situ stiffening induced ECM remodelling and invasion of normal mammary acini was driven by beta1 integrin-FAK-Piezo1 pathway with Piezo1 specifically being downstream of integrin activation and signalling.

Kabilan then followed the process of in-situ stiffening induced changes in acini morphology and ECM properties over time and found interesting and "dynamic" changes in relative ECM enrichment which coincided with different stages of growth and the onset of invasion

Interestingly, he found several differences in basement membrane and ECM(Fibronectin) enrichment and organisation between acini embedded in in-situ stiffened gels compared to acini formed from single MCF10A cells embedded in stiff gels from Day 1 (see below)

Here Kabilan first embedded single MCF10A cells in a soft interpenetrating network hydrogel system and allowed it to form a normal mammary acini with its own native ECM environment. He then in-situ stiffened these gels thus mimicking tumour growth and invasion on normal 3D structures-