Abstract
Compartmentalization is a characterizing feature of complexity in cells, used to organize their biochemistry. Membrane-bound organelles are most widely known, but non-membrane-bound liquid organelles also exist. These have recently been shown to form by phase separation of specific types of proteins known as scaffolds. This forms two phases: a condensate that is enriched in scaffold protein separated by a phase boundary from the cytoplasm or nucleoplasm with a low concentration of the scaffold protein. Phase separation is well known for synthetic polymers, but also appears important in cells. Here, we review the properties of proteins important for forming these non-membrane-bound organelles, focusing on the energetically favourable interactions that drive condensation. On this basis we make qualitative predictions about how cells may control compartmentalization by condensates; the partition of specific molecules to a condensate; the control of condensation and dissolution of condensates; and the regulation of condensate nucleation. There are emerging data supporting many of these predictions, although future results may prove incorrect. It appears that many molecules may have the ability to modulate condensate formation, making condensates a potential target for future therapeutics. The emerging properties of condensates are fundamentally unlike the properties of membrane-bound organelles. They have the capacity to rapidly integrate cellular events and act as a new class of sensors for internal and external environments.This article is part of the theme issue ‘Self-organization in cell biology’.
Highlights
In order to organize their biochemistry, cells form compartments
Many cellular compartments are not bound by membranes, and these tend to assemble and disassemble rapidly. They can form in the cytoplasm or nucleoplasm, but here, for simplicity, we generally refer to the cytoplasm
From the types of interaction, we suggest it is becoming possible to make specific predictions: the posttranslational modifications that will promote condensation or dissolution, which molecules would preferentially partition to a condensate, and how those molecules may nucleate, stabilize or destabilize a droplet depending on their properties
Summary
In order to organize their biochemistry, cells form compartments. Many are bound by membranes, and these tend to be stable. Many cellular compartments are not bound by membranes, and these tend to assemble and disassemble rapidly They can form in the cytoplasm or nucleoplasm, but here, for simplicity, we generally refer to the cytoplasm. We refer to this class of non-membrane-bound compartments as biomolecular condensates, or condensates for convenience [7]. To a cell, these condensates may seem solid or liquid. We discuss how our current knowledge of the protein interactions driving condensate formation allows us to begin to predict how a cell may exploit a condensate as a biochemical compartment Many of these predictions are built on incomplete evidence, or a greatly simplified view of the complex environment of a living cell that is decidedly out of equilibrium, but they provide an equilibrium touchstone for framing a discussion about non-equilibrium effects
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