Mechanically sensitive membrane channels, such
as the widely studied MscL, are crucial in maintaining the viability of
living cells. These channels are typically made up of a 5-8
transmembrane proteins that form a barrel-like assembly. They allow
fluid to flow through
the cell membrane in their open (active) state but either restricted
it, or suppressed it entirely, in their closed (inactive) state (see
Fig.1). As well as maintaining osmotic balance mechanosenstive channels
play important sensing roles in touch, hearing, turgor control in plant
cells etc.  Fig.1A structural model of
gating in MscL. from Perozo etal. Nature 418,95
(2002)
Gating-by-tilt of
mechanosensitive membrane channel The general conclusion of the
above model is that any membrane protein possessing distinct
confomations that couple differently to the surrouding membrane should
be sensitive to the membrane structure and mechanical properties. The
question is whether this sensitivity can be experimentally observed,
and whether it can serve a physiological role. We have applied this
concept to ion channels that permit the selective passage of ions
through the membrane. We have conducted a detailed study to quantify
the mechano-sensitivity of ion channel for several classes of channel
conformation changes (Fig.5) and resulting imposed deformations in the
lipid bilayer. Our study show that the lipid bilayer should
suffers deformations with a characteristic free-energy scale of 10kBT,
which is comparable to the voltage-dependent part of the total gating
energy. These deformations could play an important role in the overall
free-energy budget of gating and modify the typical transmembrane
potential for which channel open (activation voltage). As a result,
channel activity will depend upon mechanical membrane parameters such
as tension and leaflet thickness. We further argue that the membrane
deformation around any channel can be divided into three generic
classes of deformation that exhibit different mechanosensitive
properties. While the effect of membrane thickness on the opening
probability of several channels have been reported (Goulian etal. Biophys. J. 74, 328 (1998) for Gramicidin and Perozo etal.
Nat. Struc. Biol. 9, 697 (2002) for MscL), this line of
investigation suggests experiments that one could discern
the dominant deformation imposed upon the membrane as a result of
channel gating, thus providing clues as to the channel deformation
induced by the stimulus.
Membrane mechanics as a probe of ion-channel gating mechanisms |
The transition from
"mostly closed" to "mostly open" states is
gated by the mechanical tension of the membrane. In a simplified
two-state model, the channel may be in two configurations, separated by
an energy difference (Fig.2). At thermal equilibrium, the fraction of
open to close channels is
the
Boltzmann exponential of this energy difference. The closed state is
preferred at low tension, while high tension favores the open state. It
is generally assumed that the mechanism by which the channel opens is a
simple dilation (Fig.3a), for which the work available for providing
the energy for the transition is proportional to the membrane tension
and the change in area between the close and open states. The larger
the work, the more precise and sensitive the channel may be.
Simple dilation has inherent limitation due to the size of the channel
(~5nm) and of the area increase (~20nm2), which for a gating
tension of order 2 10-3 N/m, provides an energy of order 10
kBT.
