Connections between physics and metabolism in brain functions

Abstract

Advances in molecular biology have shaped our understanding of cellular biology. Yet, this molecular-centric approach has overshadowed the role of physical processes governing cellular homeostasis. In genetic disor-ders, particularly inherited metabolic diseases, phenotypic heterogeneity cannot solely be explained by genetic variants. Mechanical properties of cells and tissues may account for this variability, given the interplay between biological and physical cues in metabolic regulations. In July 2024, we organized an international symposium with world experts in physics, chemistry, and neurobiology to explore the physical regulation of brain metabolism in health and disease. Topics included mechanotransduction in neurodevelopment and brain aging, the physics of neurotransmission and cellular trafficking, and emerging methods to model cellular metabolism, analyze single-cell mechanical and transcriptional signals, and track nanoparticles in intact brain tissue. This effort aims to foster an interdisciplinary framework for neuroscience and train scientists across disciplines, while integrating art to stimulate creativity and integrative thinking.