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Andrea Sottini

Publications and source records attributed to Andrea Sottini.

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Material properties of biomolecular condensates emerge from nanoscale dynamics

Biomolecular condensates form by phase separation of biological polymers and have important functions in the cell $-$ functions that are inherently connected to their physical properties. A remarkable aspect of such condensates is that their viscoelastic properties can vary by orders of magnitude, but it has remained unclear how these pronounced differences are rooted in the nanoscale dynamics at the molecular level. Here we investigate a series of condensates formed by complex coacervation that span about two orders of magnitude in molecular dynamics, diffusivity, and viscosity. We find that the nanoscale chain dynamics on the nano- to microsecond timescale can be accurately related to both translational diffusion and mesoscale condensate viscosity by analytical relations from polymer physics. Atomistic simulations reveal that the observed differences in friction $-$ a key quantity underlying these relations $-$ are caused by differences in inter-residue contact lifetimes, leading to the vastly different dynamics among the condensates. The rapid exchange of inter-residue contacts we observe may be a general mechanism for preventing dynamic arrest in compartments densely packed with polyelectrolytes, such as the cell nucleus.

physics.bio-ph

Leveraging partial coherence in interferometric microscopy to enhance nanoparticle detection sensitivity and throughput

Interferometric-based microscopies stand as powerful label-free approaches for monitoring and characterising chemical reactions and heterogeneous nanoparticle systems in real time with single particle sensitivity. Nevertheless, coherent artifacts, such as speckle and parasitic interferences, together with limited photon fluxes from spatially incoherent sources, pose an ongoing challenge in achieving both high sensitivity and throughput. In this study, we systematically characterise how partial coherence affects both the signal contrast and the background noise level; thus, it offers a route to improve the signal-to-noise ratio from single nanoparticles (NPs), irrespective of their size and composition; or the light source used. We first validate that lasers can be modified into partially coherent sources with performance matching that of spatially incoherent ones; while providing higher photon fluxes. Secondly, we demonstrate that tuning the degree of partial coherence not only enhances the detection sensitivity of both synthetic and biological NPs, but also affects how signal contrasts vary as a function of the focus position. Finally, we apply our findings to single-protein detection, confirming that these principles extend to differential imaging modalities, which deliver the highest sensitivity. Our results address a critical milestone in the detection of weakly scattering NPs in complex matrices, with wide-ranging applications in biotechnology, nanotechnology, chemical synthesis, and biosensing; ushering a new generation of microscopes that push both the sensitivity and throughput boundaries without requiring beam scanning.

physics.optics