Emergence of collective oscillations in adaptive cells

TL;DR

This paper uncovers common principles behind collective cell oscillations, highlighting the role of adaptation, phase matching, and signal relay gain, and provides predictive conditions for oscillation onset and frequency.

Contribution

It introduces a unified framework linking cellular adaptation and phase matching to collective oscillations, applicable across diverse biological systems.

Findings

Positive intracellular signal relay is essential for oscillations.

Phase matching enables energy flow from cells to signals.

Derived conditions predict oscillation onset and frequency.

Abstract

Collective oscillation of cells in a population has been reported under diverse biological contexts and with vastly different molecular constructs. Could there be common principles similar to those that govern spontaneous oscillation in mechanical or electrical systems? Here, we answer this question in the affirmative by categorising the response of individual cells against a time-varying signal. A positive intracellular signal relay of sufficient gain from participating cells is required to sustain the oscillations, together with phase matching. The two conditions yield quantitative predictions for the onset cell density and frequency in terms of measured single-cell and signal response functions. Through mathematical constructions, we show that cells that adapt to a constant stimulus fulfil the phase requirement by developing a leading phase in an "active" frequency window that enables cell-to-signal energy flow. Analysis of dynamical quorum sensing in several cellular systems with increasing biological complexity reaffirms the pivotal role of adaptation in powering oscillations in an otherwise dissipative cell-to-cell communication channel. The physical conditions identified can be used to design synthetic oscillatory systems