Abstract
Although liquid–liquid phase separation of cytoplasmic or nuclear components in cells has been a major focus in cell biology, it is only recently that the principle of phase separation has been a long-standing concept and extensively studied in biomembranes. Membrane phase separation has been reconstituted in simplified model systems, and its detailed physicochemical principles, including essential phase diagrams, have been extensively explored. These model membrane systems have proven very useful to study the heterogeneity in cellular membranes, however, concerns have been raised about how reliably they can represent native membranes. In this review, we will discuss how phase-separated membrane systems can mimic cellular membranes and where they fail to reflect the native cell membrane heterogeneity. We also include a few humble suggestions on which phase-separated systems should be used for certain applications, and which interpretations should be avoided to prevent unreliable conclusions.
Highlights
Membranes are complex structures comprised primarily of lipids and proteins
We have focused on microscopic phase separation in model membrane systems
On top of plasma membrane (PM)’s own complexity, there is a complex interplay between PM and other cellular elements such as cytoskeleton and glycocalyx that are usually missing in model membranes
Summary
Membranes are complex structures comprised primarily of lipids and proteins. membranes have been a major research focus for over a century [1], the exact lipid and protein composition of plasma membrane (PM) is still under investigation. Hundreds of different lipids and membrane proteins have been identified, and our understanding of their function is continuously rising [3,4] This incredible complexity of PM constitutes one of the most fundamental questions in cell biology: Why do we have so many lipids? Thanks to critical experiments in the following years, the main methodology to determine raft association of proteins, namely detergent resistance assay, was found to be unreliable and largely nonreproducible This was a major setback for the raft concept, biophysical investigations of the core idea of lateral membrane heterogeneity did not vanish (unlike biologists’ enthusiasm to find their proteins in lipid rafts). We will discuss the phase separation in these model systems and the discrepancies in their biophysical properties
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
