Robustness analysis of cellular memory in an autoactivating positive feedback system.

Area of Science:

• Cellular biology
• Systems biology
• Theoretical biology

Background:

• Cellular memory is a fundamental biological process observed across various cell types.
• Transcriptional positive feedback systems are known to exhibit bistability, a prerequisite for memory.
• Understanding the resilience of cellular memory to internal fluctuations is critical.

Purpose of the Study:

• To investigate the robustness of cellular memory within a transcriptional positive feedback system subjected to intrinsic noise.
• To quantify the impact of system parameters on memory stability and persistence.
• To provide a dynamical systems perspective on the role of feedback loops in epigenetic memory.

Main Methods:

• Numerical simulations of a transcriptional positive feedback system.
• Theoretical analysis using concepts from dynamical systems theory.
• Quantification of memory robustness using metrics like memory robustness index and mean first-passage time.

Main Results:

• The system, without noise, can establish two stable steady states, enabling memory function.
• Increased cell size and binding cooperativity significantly enhance memory storage capacity.
• An additional positive feedback loop bolsters memory persistence, whereas a negative feedback loop destabilizes it.
• Simulation outcomes align with existing experimental observations.

Conclusions:

• Cellular memory robustness is significantly influenced by system parameters like cell size and cooperativity.
• Positive feedback loops are key for establishing and maintaining cellular memory, with multiple loops enhancing persistence.
• Negative feedback loops can compromise the stability of cellular memory.
• Dynamical systems principles offer valuable insights into the mechanisms underlying epigenetic memory.