CONNECTING CELLULAR WATER DYNAMICS TO DRUG ACTION: A NEUTRON SCATTERING PERSPECTIVE

Water is the dominant molecular component of living cells, yet its dynamical behaviour remains an almost unexplored probe of cellular physiology and drug response. In complex intracellular environments, water exists in heterogeneous populations, ranging from bulk-like to highly confined interfacial states, whose mobility reflects membrane organization, macromolecular crowding, and cytoskeletal dynamics. This talk explores how modern neutron scattering can transform our understanding of therapeutic mechanisms by positioning cellular water as a direct biophysical linker to drug action.

Focusing on A549 lung epithelial cells exposed to tocilizumab (TCZ), a monoclonal antibody used to mitigate severe inflammatory responses, we combine quasi-elastic neutron scattering (QENS) with inelastic neutron spectroscopy to probe cellular dynamics across complementary temporal and spatial scales. QENS resolves nanoscale translational and rotational motions of intracellular water, while TOSCA provides vibrational fingerprints of hydration environments, biomolecular flexibility, and cytoskeletal structure. Together, these approaches allow us to quantify how free versus nanoparticle-encapsulated TCZ modulates intracellular water populations and cellular mechanical states.

Integrated with Raman spectroscopy, thermal analysis, and Cryo-Soft X-ray Tomography, our studies reveal that TCZ treatment induces measurable changes in the balance between bulk and interfacial water, consistent with altered membrane interactions, intracellular crowding, and structural remodelling. Nanoparticle-mediated delivery further modifies these effects, suggesting that drug formulation directly impacts cellular biophysics beyond pharmacology alone. This work establishes a framework in which water dynamics function not merely as a solvent, but as a sensitive functional biomarker linking molecular therapeutics to whole-cell physical state. By bridging neutron spectroscopy, nanomedicine, and cellular biophysics, these studies open new opportunities for drug efficacy and delivery platforms to redefine therapeutic evaluation through the lens of physical biology.

This work was supported by Erasmus+ International Credit Mobility Program (European Commission) and by Danscatt.