Abstract
The shape of lipids has long been suspected to be a critical determinant for the control of membrane fusion. To experimentally test this assertion, we used conical and malleable lipids and measured their influence on the fusion kinetics. We found that, as previously suspected, both types of lipids accelerate fusion. However, the implicated molecular mechanisms are strikingly different. Malleable lipids, with their ability to change shape with low energy cost, favor fusion by decreasing the overall activation energy. On the other hand, conical lipids, with their small polar head relative to the area occupied by the hydrophobic chains, tend to make fusion less energetically advantageous because they tend to migrate towards the most favorable lipid leaflet, hindering fusion pore opening. They could however facilitate fusion by generating hydrophobic defects on the membranes; this is suggested by the similar trend observed between the experimental rate of fusion nucleation and the surface occupied by hydrophobic defects obtained by molecular simulations. The synergy of dual-process, activation energy and nucleation kinetics, could facilitate membrane fusion regulation in vivo.
Highlights
Membrane fusion is one of the means used by cells, organelles and lipid-bound objects to interact and transmit information (Martens and McMahon, 2008)
Erratic membrane fusion is prevented by the energy barriers that ought to be overcome on the pathway to fusion (Kuzmin et al, 2001)
We recently showed experimentally on membranes made of a single lipid type (DOPC or POPC, see Material and Methods for the definition of lipid acronyms) that the fusion kinetics are well-described by an Arrhenius law, i.e. that the energy landscape for fusion can be approximated by a single energy barrier over a range of physiologically relevant temperatures (27°C–47°C) (FrançoisMartin et al, 2017)
Summary
Membrane fusion is one of the means used by cells, organelles and lipid-bound objects to interact and transmit information (Martens and McMahon, 2008). Communication takes place as the contents of the newly fused compartments freely mix or react after the lipids leaflets of two compartments have coalesced to form a unique and continuous membrane. Erratic membrane fusion is prevented by the energy barriers that ought to be overcome on the pathway to fusion (Kuzmin et al, 2001). It is quite commonly assumed that fusion proceeds in steps: first, through the approach and binding of the apposed membranes, by the formation of an hemifused-like structure in which only the outer monolayers have fused, and by the completion of fusion through the merging of the inner monolayers thereby forming a fusion pore (Figure 1). In the case of intracellular vesicular transport and exocytosis, SNARE proteins that are present on two apposing membranes spontaneously assemble into an
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