Matters of Life and Death in Computational Cell Biology

TL;DR

This paper emphasizes the importance of biophysical constraints in computational cell biology, proposing a new theoretical framework centered on cellular viability and geometric structures to understand life-death boundaries.

Contribution

It introduces a foundational approach to model cellular viability using geometric structures and emergent individual models, addressing a gap in systematic implementation of biophysical constraints.

Findings

Geometric structures can distinguish regions with similar survival outcomes.

Proposes that emergent individual models help understand life's limits.

Lays groundwork for a theory of cellular viability.

Abstract

Nearly all cell models explicitly or implicitly deal with the biophysical constraints that must be respected for life to persist. Despite this, there is almost no systematicity in how these constraints are implemented, and we lack a principled understanding of how cellular dynamics interact with them and how they originate in actual biology. Computational cell biology will only overcome these concerns once it treats the life-death boundary as a central concept, creating a theory of cellular viability. We lay the foundation for such a development by demonstrating how specific geometric structures can separate regions of qualitatively similar survival outcomes in our models, offering new global organizing principles for cell fate. We also argue that idealized models of emergent individuals offer a tractable way to begin understanding life's intrinsically generated limits.