Josh V. Vermaas and Emad Tajkhorshid.
A microscopic view of phospholipid insertion into biological
membranes.
Journal of Physical Chemistry B, 118:1754-1764, 2014.
(PMC: PMC3933253)
VERM2014-ET
Understanding the process of membrane insertion is an essential step in developing a
detailed mechanism, for example, for peripheral membrane protein association and
membrane fusion. The highly mobile membrane mimetic (HMMM) has been used to
accelerate the membrane association and binding of peripheral membrane proteins in
simulations by increasing the lateral diffusion of phospholipid headgroups while retaining
an atomistic description of the interface. Through a comparative study, we assess the
difference in insertion rate of a free phospholipid into an HMMM as well as into a
conventional phospholipid bilayer and develop a detailed mechanistic model of free
phospholipid insertion into biological membranes. The mechanistic insertion model shows
that successful irreversible association of the free phospholipid to the membrane interface,
which results in its insertion, is the rate-limiting step. Association is followed by
independent, sequential insertion of the acyl tails of the free phospholipid into the
membrane, with splayed acyl tail intermediates. Use of the HMMM is found to replicate the
same intermediate insertion states as in the full phospholipid bilayer; however, it
accelerates overall insertion by approximately a factor of 3, with the probability of
successful association of phospholipid to the membrane being significantly enhanced.
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