Breaking down calcium timing in heterogenous cells populations

Calcium controls a large number of cellular processes at different scales. Decades of studies have pointed out theimportance of calcium signaling in regulating differentiation, apoptosis, mitosis and functions such as secretion,muscle contraction and memory. The space-time structure of calcium signaling is central to this complexregulation. In particular, cells within organisms behave as clocks beating their own biological time, although inseveral cases they can synchronize across long distances leading to an emergent space-time dynamics which iscentral for single cell and organ functioning. We use a mathematical model built on published experimental dataof hepatic non-excitable cells, analyzing emerging calcium dynamics of cells clusters composed both of normallyfunctioning cells and pathological aggregates. Calcium oscillations are investigated by varying the severity ofdysfunction and size of pathological aggregate. We show how strong and localized heterogeneity in cellularproperties can profoundly alter organized calcium dynamics leading to sub-populations of cells which createtheir own coordinated dynamical organization. Our simulations of Ca2þ signals reveal how cell behaviors differand are related to intrinsic time signals. Such different cells clusters dynamically influence each other so thatnon-physiological although organized calcium patterns are generated. This new reorganization of calcium activitymay possibly be a precursor of cancer initiation.