Extra-cellular Matrix in cell aggregates is a proxy to mechanically control cell proliferation and motility

Abstract

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions. To perceive mechanical perturbations of different types and magnitudes, tissues need appropriate detectors, with a compliance that matches the perturbation amplitude. By comparing results of selective osmotic compressions of cells within multicellular aggregates with small osmolites and global aggregate compressions with big osmolites, we show that global compressions have a strong impact on the aggregates growth and internal cell motility, while selective compressions of same magnitude have almost no effect. Both compressions alter the volume of individual cells in the same way but, by draining the water out of the extracellular matrix, the global one imposes a residual compressive mechanical stress on the cells while the selective one does not. We conclude that, in aggregates, the extracellular matrix is as a sensor which mechanically regulates cell proliferation and migration in a 3D environment.

Theca cell mechanics and tissue pressure regulate mammalian ovarian folliculogenesis

“…Importantly, we found that global compression of follicles leads to cytoplasmic YAP localization and reduced proliferation of GCs, similar to what has been reported for cancer cell spheroids 70 . Here, we propose that the increase in tissue packing may promote GC interactions to activate contact inhibition signals of proliferation 71 .…”

Cells under pressure

“…However, full three-dimensional control of uniform compression of tumor spheroids has not been achieved to date. Now, in eLife, Giovanni Cappello, Pierre Recho and colleagues from the Université Grenoble Alpes, the Université de Lyon and the Collège de France – including Monika Dolega as first author – report a new way to study the impact of solid stress on tumor spheroids ( Dolega et al, 2021 ).…”