Shape bistability of a membrane neck: A toggle switch to control vesicle content release

Abstract

Shape dynamics and permeability of a membrane neck connecting a vesicle and plasma membrane are considered. The neck is modeled by a lipid membrane tubule extended between two parallel axisymmetric rings. Within a range of lengths, defined by system geometry and mechanical properties of the membrane, the tubule has two stable shapes: catenoidal microtubule and cylindrical nanotubule. The permeabilities of these two shapes, measured as ionic conductivity of the tubule interior, differ by up to four orders of magnitude. Near the critical length the transitions between the shapes occur within less than a millisecond. Theoretical estimates show that the shape switching is controlled by a single parameter, the tubule length. Thus the tubule connection can operate as a conductivity microswitch, toggling the release of vesicle content in such cellular processes as ''kiss-and-run'' exocytosis. In support of this notion, bistable behavior of membrane connections between vesicles and the cell plasma membrane in macrophages is demonstrated.

Force Barriers for Membrane Tube Formation

“…The value of the overshoot force (the force barrier for tube formation), F over , was predicted to be 13% higher than F 0 [14,16]. Under certain conditions, the shape transition was furthermore predicted to be discontinuous (first order) [15,16,18]. In reality, a force is, however, never applied to a single point as was assumed in these theoretical studies.…”

“…Before the tube formation transition, the shape of the membrane is best described by a catenoid [14,16,18] imposed on the sphere of the vesicle. In our experiments the end ring of this catenoid can be identified as the rim of the patch, and it can support forces up to about 2R p 0:5F 0 R p =R 0 .…”

The evidence for open and closed exocytosis as the primary release mechanism

“…This indicates that at the end of a release event the vesicle matrix is still mostly covered by membrane, and not exposed to the extracellular environment, suggesting that full fusion is unlikely for these events. Previous work by Frolov et al focused on the point connecting the vesicle to the plasma membrane, called the neck (Frolov et al 2003). Here model systems of the neck were created using a patch pipette and a stable Teflon ring.…”

“…This work further suggests a mechanism for providing a transient opening of the neck, similar to what may be present during 'kiss-and-run' exocytosis, where the permeability of the neck can be 'toggled' by the different stable states, and might even 'flicker'. This concept might play an important physiological role, maintaining the compartments where two environments meet (Frolov et al 2003).…”

Vesicle shape, molecular tilt, and the suppression of necks

“…Narrow necks with small mean curvature but large negative Gaussian curvature are relevant to biological membranes that compartmentalize through budding, since this neck geometry allows separate membranebound compartments to be budded off, while avoiding high-energy membrane shapes. Neck formation is universal and crucial to the phenomena of endo-and exocytosis [7,8], viral entry and budding, the traffic of continual fusion and fission of vesicle and Golgi membrane, and the interconnections between Golgi stacks [9] and between the smooth and rough endoplasmic reticulum. Because of the close association of these phenomena with cell function, it is crucial to understand the forces on membrane necks and the constraints on their formation.…”