Gehrer, S. | Search bioRxiv

bioRxiv2023

Morphology as indicator of adaptive changes of model tissues in osmotically and chemically changing environments

We investigate the formation and maintenance of the homeostatic state in the case of 2D epithelial tissues following an induction of hyperosmotic conditions, using media enriched with 80 to 320 mOsm of mannitol, NaCl, and urea. We characterise the changes in the tissue immediately after the osmotic shock, and follow it until the new homeostatic state is formed. We characterise changes in cooperative motility and proliferation pressure in the tissue upon treatment with the help of a theoretical model based on the delayed Fisher-Kolmogorov formalism, where the delay in density evolution is induced by the the finite time of the cell division. Finally we explore the adaptation of the homeostatic tissue to highly elevated osmotic conditions by evaluating the morphology and topology of cells after 20 days in incubation. We find that hyperosmotic environments together with changes in the extracellular matrix induce different mechanical states in viable tissues, where only some remain functional. The perspective is a relation between tissue topology and function, which could be explored beyond the scope of this manuscript. O_LIExperimental investigation of morphological effect of change of osmotic conditions on long-term tissue morphology and topology C_LIO_LIEffect of osmotic changes on transient tissue growth behaviour C_LIO_LIAnalysis of recovery process of tissues post-osmotic-shock C_LIO_LIToxicity limits of osmolytes in mid- to long-term tissue evolution C_LIO_LITissue adaptation to physiological changes in environment C_LIO_LILong-term tissue stabilisation under altered osmotic conditions. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/524301v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@826d28org.highwire.dtl.DTLVardef@cc7f35org.highwire.dtl.DTLVardef@1b370fborg.highwire.dtl.DTLVardef@1bea90e_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2021

On the mechanical regulation of epithelial tissue homeostasis

Despite recent efforts to understand homeostasis in epithelial tissues, there are many unknowns surrounding this steady state. It is considered to be regulated by mechanoresponse, but unlike for single cells, this remains heavily debated for tissues. Here, we show that changes in matrix stiffness induce a non-equilibrium transition from tubular to squamous Madin-Darby Canine Kidney II tissues. Nonetheless, despite different cell morphologies and densities, all homeostatic tissues display equivalent topologies, which, hence, must be actively targeted and regulated. On the contrary, the mechanoresponse induces dramatic changes in the large-scale organization of the colonies. On stiff gels, this yields an unreported cooperative state of motile cells displaying higher densities than in the arrested homeostatic state. This suggests a more complex relation between cell density and motility than previously anticipated. Our results unequivocally relate the mechanosensitive properties of individual cells to the evolving macroscopic structures, an effect that could be important for understanding the emergent pathologies of living tissues.

biophysics↗