Intracellular Molecular Dynamics Progressively Change during Carcinogenesis Revealed by Elastic and Quasi-Elastic Neutron Scattering

Abstract Cancer has traditionally been studied from molecular and genetic perspectives, and more recently, increasing attention has been directed toward its physical aspects. The intrinsically disordered proteome is altered in cancer cells compared to normal cells. Nevertheless, how the emergence of these proteins is associated with the intracellular physical environment remains unknown. Here, we investigated intracellular dynamics during tumorigenesis using normal, precancerous, and tumor-derived organoids by elastic incoherent neutron scattering (EINS) and quasi-elastic neutron scattering (QENS). EINS analysis revealed a decrease in atomic mean-square displacement from control to precancerous and tumor organoids. In contrast, QENS analysis demonstrated gradual decreases in both the elastic fraction and correlation time, indicating that a larger fraction of intracellular molecules undergoes faster motions during tumorigenesis. These findings suggest that the intracellular physical state is progressively remodeled during cancer development and provide a physical perspective of tumorigenesis.