Abstract
BackgroundOver the past decade, it has become apparent that specialised membrane microdomains, commonly called rafts, where lipids like sphingolipids and cholesterol are arranged compactly in a liquid ordered phase are involved in cell signalling.HypothesisThe core of the hypothesis presented here is that resting cells may actively maintain their plasma membrane in liquid phase, corresponding to a metastable thermodynamic state. Following a physiological stimulus such as ligands binding to their membrane receptors, the tendency of membrane components to undergo a localised transition towards a gel state would increase, resulting in initial minute solid structures. These few membrane components having undergone a liquid to solid state transition, would then act as seeds for the specific recruitment of additional membrane components whose properties are compatible with the crystalline growth of these initial docks. Cells could therefore be using the propensity of lipids to assemble selectively to generate stable platforms of particular cellular components either for intra-cellular transport or for signal transduction.Testing the hypothesiscould presumably be done via biophysical approaches such as EPR spin labelling, X-ray diffraction or FRET coupled to direct microscopic observation of cells to which very localized stimuli would be delivered.ImplicationsSuch a model of selective growth of membrane docks would provide an explanation for the existence of different types of microdomains, and for the fact that, depending on the state of the cells and on the procedures used to isolate them, membrane microdomains can vary greatly in their properties and composition. Ultimately, a thorough understanding of how and why lipid domains are assembled in biological membranes will be essential for many aspects of cell biology and medicine.
Highlights
Over the past decade, it has become apparent that specialised membrane microdomains, commonly called rafts, where lipids like sphingolipids and cholesterol are arranged compactly in a liquid ordered phase are involved in cell signalling.Hypothesis: The core of the hypothesis presented here is that resting cells may actively maintain their plasma membrane in liquid phase, corresponding to a metastable thermodynamic state
This conceptual definition has evolved towards a more biochemical one, and the term raft is nowadays most often used to describe a fraction of cellular membranes that remain insoluble in non-ionic detergents at 4°C, have a lipid
There is an increased thickness of the membrane, but the average speed of molecules is comparable to that seen in the liquid disordered state (Ld) phase.) For both these liquid phases, the thermal energy of individual molecules is superior to the one resulting from their interaction with their neighbours
Summary
It has become apparent that specialised membrane microdomains, commonly called rafts, where lipids like sphingolipids and cholesterol are arranged compactly in a liquid ordered phase are involved in cell signalling.Hypothesis: The core of the hypothesis presented here is that resting cells may actively maintain their plasma membrane in liquid phase, corresponding to a metastable thermodynamic state. Like specks of dust on glass walls for the formation of bubbles in champagne and like impurities for formation of ice crystals in water, I propose that, despite being thermodynamically favourable, truly organized structures in biological membranes may develop only after an initial seed has been put in place.
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