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Is Ficoll Colloid or Polymer? A Multi-Technique Study of a Prototypical Excluded-Volume Macromolecular Crowder



Venketesh Ranganathan, Saman Bazmi, Stefan Wallin, Yun Liu, Anand Yethiraj


The in-cell environment is crowded with macromolecules, and the consequent reduction in free volume, the hard-sphere paradigm, is central to understanding macromolecular motions. A much-used model crowder, Ficoll, often assumed to be a compact, if not rigid, colloidal particle, is studied by rheology, small-angle neutron scattering, nuclear magnetic resonance diffusometry and relaxometry. We find that the Ficoll suspension viscosity scales linearly with concentration cF in the dilute limit and as ∼ c3.8F at high cF, i.e, consistent with the 15/4 (de Gennes) scaling for a reptating polymer. The form factor of Ficoll, obtained via small-angle neutron scattering (SANS), resembles either a Gaussian polymer or a soft polymer blob. From NMR diffusion measurements, we obtain an effective volume fraction for Ficoll that accounts for Ficoll-bound water in two ways, and show each results in a volume occupancy of 60 to 70 % in the crowding limit, much larger than the traditionally reported values of around 30 %. Persisting with the colloid paradigm, we examine the dependence of the zero-q structure factor, obtained via SANS, in terms of this effective volume fraction. Ficolls are far from hard sphere; indeed only a combination of particle softness and inter-particle attractions, quantified using a computational model, can replicate the experimental S(0). The stark difference between effective and traditional volume occupancies will affect the interpretation of previous experiments on macromolecular crowding and might explain the intriguing non-monotonicity observed in the dependence of protein relaxation rates on crowder concentration.
Journal of American Chemical Society


SANS, colloid, polymer, crowding, viscosity


Ranganathan, V. , Bazmi, S. , Wallin, S. , Liu, Y. and Yethiraj, A. (2022), Is Ficoll Colloid or Polymer? A Multi-Technique Study of a Prototypical Excluded-Volume Macromolecular Crowder, Journal of American Chemical Society (Accessed May 19, 2024)


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Created October 2, 2022, Updated November 29, 2022