Stress distributions and cell flows in a growing cell aggregate

Abstract

We discuss the short-time response of a multicellular spheroid to an external pressure jump. Our experiments show that 5 min after the pressure jump, the cell density increases in the centre of the spheroid but does not change appreciably close to the surface of the spheroid. This result can be explained if the cells are polarized which we show to be the case. Motivated by the experimental results, we develop a theory for polarized spheroids where the cell polarity is radial (except in a thin shell close to the spheroid surface). The theory takes into account the dependence of cell division and apoptosis rates on the local stress, the cell polarity and active stress generated by the cells and the dependence of active stress on the local pressure. We find a short-time increase of the cell density after a pressure jump that decays as a power law from the spheroid centre, which is in reasonable agreement with the experimental results. By comparing our theory to experiments, we can estimate the isotropic compression modulus of the tissue.

Active gel physics

“…During such processes, cells divide, rearrange and exhibit a complex collective dynamics, which on large scales can be described by generalized hydrodynamics. Even though the interacting elements are now cells rather than filaments, the same generic equations discussed for active gels apply again in this large-scale limit because the conservation laws and symmetries are similar [69][70][71] . In particular, cell collections can have polar or nematic symmetries 72 .…”

Effect of an osmotic stress on multicellular aggregates

“…As the ECM is rather compliant [29] and highly permeable to water, it is more likely to be compressed than the embedded cells. Actually, neither the over-reaction of the spheroid nor the inhomogeneous response can be totally inferred from the response of single cells or from the presence of ECM in the core, but it might originate from an active response of the cells inside the aggregate as recently suggested [30]. …”

Survival of the Fittest: Essential Roles of Cell Competition in Development, Aging, and Cancer

“…Through which mechanisms could competition promote tumor expansion? The resistance of the extracellular matrix and of the surrounding tissue to tumor growth generates strong mechanical stress [55,62], which should feedback negatively on the survival and growth rate of tumoral cells [82][83][84]. Elimination of surrounding cells by cell competition could release space at the tumor boundaries and promote its expansion ( Figure 4C).…”