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Liquid-Liquid Crystalline Phase Separation of Amyloid Fibrils

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Liquid-Liquid phase separation of macromolecules is ubiquitous in nature and implies, in the most common form, the demining of a macromolecule rich-phase (often as droplets) from a macromolecules-depleted continuous phase. Liquid-liquid phase separation in the context of biomacromolecules has been shown to be at the center of important cellular processes and is involved in the formation of the so-called membraneless organelles. In the case of filamentous colloids, the process is similar in the outcome, but fundamentally different in the ruling physics since the interactions among the biomacromolecules are essentially of liquid crystalline nature. We call this Liquid-Liquid Crystalline Phase Separation (LLCPS). In this talk I will discuss our recent work on amyloid liquid-liquid crystalline phase separation, including the discovery of cholesteric phases in amyloids fibrils and the new implications that this brings to the fields of liquid crystals and liquid-liquid phase separation in general. By selecting amyloid fibrils as model filamentous chiral colloids, an unprecedented breadth of liquid crystalline morphologies is observed, where up to six distinct configurations of the nematic field are observed under identical conditions. Amyloid-rich droplets also known as tactoids nucleating from an isotropic phase via liquid-liquid phase separation show homogeneous, bipolar, radial, uniaxial chiral and radial chiral nematic fields, with additional parabolic focal conics in bulk. Furthermore, tactoids of different symmetry undergo order–order transitions by flow-induced deformations of their shape. Tactoids align under extensional flow, undergoing extreme deformation into highly elongated prolate shapes, with the cholesteric pitch decreasing as an inverse power-law of the tactoids aspect ratio. Variational and scaling theories allow rationalizing the experimental evidence as a subtle interplay between surface and bulk energies and to debate on the thermodynamic nature of theses transitions. I will conclude the talk discussing the implications that LLCPS may have in the field of amyloid-based neurodegenerative diseases. References:

  1. G Nyström, M Arcari, R Mezzenga, Nature Nanotechnology 13, 330 (2018)
  2. M Bagnani, G Nyström, C De Michele, R Mezzenga, ACS Nano 13, 591 (2019)
  3. M Bagnani, P Azzari, S Assenza, R Mezzenga, Scientific Reports 9, 1-9 (2019)
  4. H Almohammadi, M Bagnani & R Mezzenga, Nature Communications 11, 5416 (2020)
  5. P Azzari, M Bagnani, R Mezzenga, Soft Matter, 17, 6627 (2021)

This talk is part of the Biophysical Seminars series.

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