Lipid Membrane Properties - An Introduction to Biological Membranes - page 182

hemi-fusion and is well-documented in model membranes. In 1986, David Siegel [28] sug-
gested that an inverted micelle structure, resembling one cylinder of H II structure, represents
the primary point defect in lamellar to H II transition (see Figure 10.9 ) [20,27] . Importantly,
factors known to promote H II phase also promote membrane fusion, and lipid-soluble fuso-
gens that induce cell

cell fusion in vitro induce H II formation in model membranes.
Assigning a non-lamellar phase role in membrane fusion was compelling since it could
start to explain some aspects of the 'lipid polymorphism' conundrum. Unfortunately, some-
times even beautiful stories disintegrate when confronted with harsh reality. Many vital
processes in cells require rapid and precise control of fusion. Biological fusion occurs on the
order of milliseconds and must be turned on and off in an orderly fashion. Model lipid vesicle
fusion is by orders of magnitude too slow to start, and once begun has no mechanism to end.
In addition it is hard to envision how H II -favoring lipids can overcome the large negative
charge repulsion on fusing-cell surfaces. Speed and control are two problems the H II -phase
lipid fusion theory could not answer. In 1993 James Rothman ( Figure 10.10 ) and colleagues
proposed a protein-based theory of membrane fusion called the SNARE hypothesis
[29,30] . In the years since its proposal, this hypothesis has successfully addressed many of
the complex problems associated with fusion. In a 2009 paper in Nature [31] , Rothman
reviewed the central aspects of how the proteins SNARE and SM (Sec1/Munc18-like) in
concert with Ca 2 þ organize lipid microdomains in fusing membranes. H II phase was not
even mentioned!

e

Cubic Phase
Another non-lamellar phase that is stable in excess (biological) levels of water includes the
cubic phases, Q 224 and Q 227 [21,25] . Like the H II phase, the cubic phase is at most a very rare
component of biological membranes and remains a phase in search of a function. Q 227 has
been proposed to repair the damage of a lipolytic agent at a local spot by forming a water-tight

FIGURE 10.9 Diagram of the mechanism of lipid-driven membrane fusion including one central H II -like
cylinder [20,27] .