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BiophysicsbioRxiv
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Particle Biology: A Perspective on a First-Principles Theory of Life

Peng Wang, Wen Li, Yishuang Cui, Hongjiao Wu, Junqing Gan, Weinan YaoiD, Ye JiniD, Yanna BiiD, Yanlei Ge, Guogui SuniD

Abstract

This Perspective formally proposes Particle Biology as a unifying theoretical framework to address the critical bottleneck in current life science research. Current life science research has reached a critical bottleneck. While the field has advanced to the study of 3D genomic spatial configurations and chromosomal organization, it remains largely descriptive and confined to the macromolecular level. This approach lacks a first-principles understanding of the underlying physical forces that drive biological processes. This Perspective formally proposes Particle Biology as a unifying theoretical framework. We establish an axiomatic system positing that life phenomena are fundamentally emergent spatiotemporal patterns of electromagnetic forces among atoms, electrons, and nuclei operating far from thermodynamic equilibrium. By defining biological states through the Biological Hamiltonian and mapping biochemical pathways to multidimensional Potential Energy Surfaces (PES), we bridge the gap between descriptive biology and predictive physics. We categorize core research technologies into three modalities--seeing, computing, and controlling particles--facilitated by advancements in Cryo-EM, AlphaFold 3, and Boron Neutron Capture Therapy (BNCT). Ultimately, the trajectory of molecular biology has evolved from cells to DNA and onto the 3D spatial genome, yet it cannot go deeper within current paradigms. The next logical evolution is to move beyond the macromolecular bottleneck to focus on the electromagnetic interactions between atoms and ions--the true Particle Biology level--to redefine disease and intervention.

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