Biological Interstitialogy: A Scale-Free Framework for Mechanistic Integration

A foundational challenge in biology is to transcend the cataloguing of components and achieve a predictive understanding of how their interactions give rise to coherent organismal functions. While network theory maps these interactions, it often treats them as abstract links, neglecting the functional role of the physical spaces in which they occur. Here, we propose Biological Interstitialogy, a paradigm that identifies the structured spaces between components—the interstices—as active determinants of biological organization. We articulate a scale-free, causal principle: interstitial Structure governs the patterns of Flow (of matter, energy, information), and these flows are the primary drivers of system-level Function. This S-F-F principle operates as a universal mechanistic chain. We marshal causal evidence across scales—from the dynamics of biomolecular condensates and the hijacking of gap junctions in cancer, to the integrative role of the brain's glymphatic system and the engineering of soil ecosystems—to validate this framework. Biological Interstitialogy reframes pathologies as "intersticiopathies" and provides a unified, mechanistic, and predictive foundation for understanding biological integration, from molecular to ecological scales, thereby opening new avenues for intervention in fields from regenerative medicine to sustainable agriculture.