Cells can secrete molecules that help each other’s replication. In cell cultures, chemical signals might diffuse only within a cell colony or between colonies. A chemical signal’s interaction length—how far apart interacting cells are—is often assumed to be some value without rigorous justifications because molecules’ invisible paths and complex multicellular geometries pose challenges. Here we present an approach, combining mathematical models and experiments, for determining a chemical signal’s interaction length. With murine embryonic stem (ES) cells as a testbed, we found that differentiating ES cells secrete FGF4, among others, to communicate over many millimeters in cell culture dishes and, thereby, form a spatially extended, macroscopic entity that grows only if its centimeter-scale population density is above a threshold value. With this ‘macroscopic quorum sensing’, an isolated macroscopic, but not isolated microscopic, colony can survive differentiation. Our integrated approach can determine chemical signals’ interaction lengths in generic multicellular communities. [Figure not available: see fulltext.].

Determining whether life can progress arbitrarily slowly may reveal fundamental barriers to staying out of thermal equilibrium for living systems. By monitoring budding yeast’s slowed-down life at frigid temperatures and with modeling, we establish that Reactive Oxygen Species (ROS) and a global gene-expression speed quantitatively determine yeast’s pace of life and impose temperature-dependent speed limits - shortest and longest possible cell-doubling times. Increasing cells’ ROS concentration increases their doubling time by elongating the cell-growth (G1-phase) duration that precedes the cell-replication (S-G2-M) phase. Gene-expression speed constrains cells’ ROS-reducing rate and sets the shortest possible doubling-time. To replicate, cells require below-threshold concentrations of ROS. Thus, cells with sufficiently abundant ROS remain in G1, become unsustainably large and, consequently, burst. Therefore, at a given temperature, yeast’s replicative life cannot progress arbitrarily slowly and cells with the lowest ROS-levels replicate most rapidly. Fundamental barriers may constrain the thermal slowing of other organisms’ lives.