Stereocilia Membrane Deformation: Implications for the Gating Spring and Mechanotransduction Channel

Abstract

In hair cells, although mechanotransduction channels have been localized to tips of shorter stereocilia of the mechanically sensitive hair bundle, little is known about how force is transmitted to the channel. Here, we use a biophysical model of the membrane-channel complex to analyze the nature of the gating spring compliance and channel arrangement. We use a triangulated surface model and Monte Carlo simulation to compute the deformation of the membrane under the action of tip link force. We show that depending on the gating spring stiffness, the compliant component of the gating spring arises from either the membrane alone or a combination of the membrane and a tether that connects the channel to the actin cytoskeleton. If a bundle is characterized by relatively soft gating springs, such as those of the bullfrog sacculus, the need for membrane reinforcement by channel tethering then depends on membrane parameters. With stiffer gating springs, such as those from rat outer hair cells, the channel must be tethered for all biophysically realistic parameters of the membrane. We compute the membrane forces (resultants), which depend on membrane tension, bending modulus, and curvature, and show that they can determine the fate of the channel.

Stiffened lipid platforms at molecular force foci

“…Such a tip link is apparently too stiff to account for the mechanical compliance associated with channel activation (33,34). Thus, this compliance arises either from the channel's own anchor to cytoskeleton or the channel's surrounding membrane (35,36), which may also be anchored. Lipids are not evenly distributed in the stereociliary membrane (37).…”

“…1A). A recent simulation evaluated the source of the gating spring for a conventional membrane, but has not incorporated the membrane stiffening by cholesterol or the likely connections to cytoskeleton (36).…”

The composition and role of cross links in mechanoelectrical transduction in vertebrate sensory hair cells

“…However, one study suggests that destroying the tip link leaves the MET channel open rather than closed, prompting the idea that the gating spring is actually a distinct structure that connects the MET channel to the internal cytoskeleton (Meyer et al, 1998). In fact, this idea may well be consistent with the proposed molecular model of the tip link whereby the link might not itself be the gating spring (see below), an idea supported by mathematical models (Powers et al, 2012). Determining the structure and molecular composition of the tip link and how it is coupled to the MET is therefore crucial to determining the mechanism of transduction.…”

Comparative Aspects of Hearing in Vertebrates and Insects with Antennal Ears

“…Since insects do not have tip links, other elements of the mechanotransduction complex, for example, the lipid bilayer and intracellular proteins in series with the transduction channels, such as the ankyrin repeat domains of the NompC mechanotransduction channel in insects, can perform the gating-spring role as well [58][59][60][61][62].…”

“…The gating-spring model describes mechanotransduction both in vertebrate and in insect ears [51,56,57]. Since insects do not have tip links, other elements of the mechanotransduction complex, for example, the lipid bilayer and intracellular proteins in series with the transduction channels, such as the ankyrin repeat domains of the NompC mechanotransduction channel in insects, can perform the gating-spring role as well [58][59][60][61][62].Although it is possible to evoke a physiological response during signal transduction by changing the activity of only a single protein -a notable example being the detection of individual photons by opsins in the retina -the collective activity of an ensemble usually provides a better signal-to-noise ratio. One hair cell may use over a hundred MET channels, located on a hair bundle's many stereocilia.…”