Membrane-Associated Self-Assembly for Cellular Decision Making

TL;DR

This paper demonstrates how spontaneous membrane-associated self-assembly can serve as a sensitive, tunable switch for cellular decision-making, rivaling active receptor signaling mechanisms.

Contribution

It introduces a passive, self-assembly-based mechanism for receptor detection, supported by analytical theory and simulations, offering new insights into cellular decision processes.

Findings

Self-assembly acts as a robust switch for receptor detection.

Analytical expressions match stochastic simulation results.

Lipids, subunits, and receptors influence decision thresholds.

Abstract

Cellular decision-making based on information received from the external environment is frequently initiated by transmembrane receptors. These receptors are known to propagate such information by triggering a series of irreversible, energy-consuming reactions. While this active mechanism ensures switch-like responses, here we show how spontaneous self-assembly of native 3D subunits on a two-dimensional substrate can similarly act as a tunable and robust switch for detecting receptors at physiological concentrations. This mechanism is much more sensitive than other passive mechanisms for receptor detection. We derive analytical expressions for the critical receptor density driving stable subunit assembly, in close agreement with stochastic reaction-diffusion simulations. The theory provides testable predictions for how lipids, subunits, and receptors each can control decision boundaries and magnitude of response.