Biological complexity: the mechanics of phase separation (Introduction)

by David Turell , Tuesday, May 09, 2023, 23:34 (354 days ago) @ David Turell

Cells conduct reactions separate from the rest of the cell by phase separation, not mechan8scaml walls:

https://www.cell.com/cell-reports-physical-science/fulltext/S2666-3864(23)00189-3?dgcid...

" We have systematically shown the effect of length on condensation of positively charged peptides and negatively charged RNA. We observed condensation for combinations of relatively short peptides and RNA, but experiments and simulations show that there does exist a lower limit in terms of RNA or peptide lengths for the systems studied here. The essential driving force for condensation is electrostatic attraction between RNA and arginine residues, counteracted by the entropic cost of condensation. The key reason for the observed length dependence is that the enthalpy of condensation scales with the number of charged units, whereas entropy scales with the number of polymers. We expect that, with peptides with lower charge density (e.g., arginine residues spaced more widely), longer peptides and/or longer RNA would be required for phase separation to be observed. On the other hand, systems with higher charge density have been proven to enable phase separation even with single nucleotides, such as UDP (−3 charge) or UTP (−4 charge), and polyR10, as observed in other work. Our study furthermore demonstrates that still shorter polymers may participate in condensates as clients or as partial drivers of condensation together with longer polymers.

" The remarkable agreement between experiment and CG simulations suggests that the computational approach could be extended to other sequences and systems as well as other dimensions in phase space, such as concentration or peptide content. The parameterization of the CG model20 explored a wide range of sequences and concentrations and accounts; for example, for the higher condensation propensity of arginine with nucleotides than lysine, as observed by Fisher and Elbaum-Garfinkle.18 However, the relative simplicity of the CG model neglects counterion effects that are known to be important factors during condensation34,35 and does not consider partial secondary structures that are present in many intrinsically disordered proteins (IDPs). Extending the model to explore the importance of these factors will be the subject of future studies.

" LLPS has practical applications for inducing high-concentration phases of certain biomolecules. The work here illustrates a quantitative framework for predicting the system components necessary for LLPS. On the other hand, this work demonstrates that a wide range of peptides and RNA can lead to LLPS. In the biological context, this means that many biomolecules may drive and/or participate in condensate formation in a dynamic manner as cellular concentrations of peptides and RNA fluctuate."

Comment: Simply charged polymers set up virtual walls around isolated reactions. This is the degree of design complexity which negates the Darwinian option of chance evolution.