Water Potential of Cell Microenvironments Modulates their Proliferation

Abstract

Microenvironmental conditions in interstitial spaces can change rapidly after inflammatory insults. Hydration potential shifts of 50-150 mmHg occur during burn and ischemia-reperfusion injury in dermal and myocardial extracellular matrices, respectively, presumably due to increased mechanical tension, fluid flux, and water activity as edema accumulates (McGee et al., Biophys J 2012;Circ Res 2012a;Wound Rep Reg 2013).While cell responses to mechanical and flow-related components of the hydration potential are increasingly studied and understood, responses to concomitant changes in water's chemical potential are not. Here, we explore its effects on HL60, an anchorage-independent, human leukemia cell line that readily differentiates towards various cell lineages. Cells (105 /ml) were grown in static suspension cultures at 37 °C, in liquid media supplemented with 2.5% fetal calf serum and at colloidosmotic pressures adjusted to between 1-100 mmHg with inert polymers. After 24 hours, the cells' growth rate changed with the water chemical potential in direct proportion to the colloidosmotic pressure of the growth solution. Linear regression analyses showed that the slope of the growth rate versus pressure was (2.4%)/day/mmHg(R2 = 0.875). The observed rate changes were independent of the physicochemical characteristics of the inert polymer; polyethyleneglycol 8000 or dextran 10 enhanced cell proliferation. Cell differentiation pathways also appeared to change as determined by the cells morphology and size in Giemsa stained cytocentrifuge preparations and further suggested by a shift to the right in the frequency-distribution of their nucleus/cytoplasm ratios. These results show that changes in water's chemical potential modulate proliferation regardless of media-stiffness or flow sensing by the cell. Hydration potential components other than the mechanical play significant roles in cells' adaptation to changes in their microenvironment.