Document Type

Theses, Ph.D

Disciplines

1.6 BIOLOGICAL SCIENCES, Biophysics, 2.10 NANO-TECHNOLOGY

Abstract

Nanoparticles have attracted significant interest due to their tunable properties and unique physicochemical characteristics, offering promising applications in drug delivery, biosensing, and diagnostics. Their use in medicine has the potential to reshape current paradigms by enabling more efficient, precise, and patient-centric approaches. Although advances in nanomaterial synthesis have rapidly expanded the library of available nanodevices, our understanding of the mechanisms that govern their behaviour at biological interfaces remains limited. Nanoparticles are similar in size to biomolecules found in biological environments, leading to complex, competitive interactions that affect their functional performance, biological fate, and acquired bioidentity. Unlike traditional small molecules, which interact through well-defined receptor–ligand or enzymatic pathways, nanoparticles engage in multi valent, surface-mediated interactions shaped by their size, shape, surface chemistry, and interfacial properties. This represents a distinct paradigm of bio–nano interactions, requiring new conceptual and analytical frameworks. Upon contact with physiological fluids, nanoparticles rapidly adsorb proteins and other biomolecules, forming the so-called protein corona. This corona alters their biological identity and governs cellular recognition, biodistribution, and downstream responses. For this reason, rational design of nanomaterials for biomedical purposes relies on a clear understanding of their interactions with biomolecules.

This thesis investigates nano–bio interactions using computational techniques across multiple scales, aiming to provide mechanistic insight into key processes relevant to the behaviour of nanomaterials in biological environments. Multiscale approaches are employed to bridge the length and time scales at which these interactions occur. Among the various open questions in the field, two dynamic processes are addressed: (i) nanoparticle diffusion in crowded biological environments, and (ii) protein adsorption onto solid surfaces, modelled in the context of protein corona formation.

In the first part of this study, mesoscale simulations are used to examine how nanoparticle diffusion is influenced by the combined effects of protein corona com viii position and medium properties. Both translational and rotational diffusion are analysed in monodisperse and polydisperse environments, across a range of crowding conditions. The results show that tracer morphology, quantified through two geometric descriptors, significantly affects mobility. The implications of these findings are discussed in terms of effective sphere models for non-spherical tracers in concentrated media.

The second part of this study employs atomistic molecular dynamics simulations to investigate the adsorption of two plasma proteins, human serum albumin (HSA) and transferrin (TRF), onto Au(111) surfaces. The analysis highlights the role of local flexibility, particularly in disordered regions, in enabling successful binding through favourable anchoring and lockdown mechanisms, with notable implications for protein re-orientation on the surface. The results are further discussed in the context of model scalability, with implications for coarse-grained and mesoscale simulations of collective protein corona dynamics over extended time scales.

Together, these findings provide detailed mechanistic insight into nanoparticle transport and protein adsorption at biologically relevant interfaces. They contribute to the development of predictive frameworks for designing nanomaterials with tailored functionalities and offer guidance for interpreting experimental observations in complex biological environments.

DOI

https://doi.org/10.21427/pbzg-3n24

Creative Commons License

Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.

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