Dynamin's helical geometry does not destabilize membranes during fission

Abstract

It is now widely accepted that dynamin-mediated fission is a fundamentally mechanical process: dynamin undergoes a GTP-dependent conformational change, constricting the neck between two compartments, somehow inducing their fission. However, the exact connection between dynamin's conformational change and the scission of the neck is still unclear. In this paper, we re-evaluate the suggestion that a change in the pitch or radius of dynamin's helical geometry drives the lipid bilayer through a mechanical instability, similar to a well-known phenomenon occurring in soap films. We find that, contrary to previous claims, there is no such instability. This lends credence to an alternative model, in which dynamin drives the membrane up an energy barrier, allowing thermal fluctuations to take it into the hemifission state.

Phosphatidic acid in membrane rearrangements

“…Membrane fission is a process that involves a splitting of one membrane-enclosed compartment into two. This process usually evolves through three steps: membrane neck formation, hemifission and formation of two separate membranes [252][253][254][255][256][257][258][259]. During membrane fission, initially saddle-shaped membrane neck forms: both monolayers remain continuous, but aqueous volume consists of two parts connected by a narrow 'capillary'.…”

Protein Amphipathic Helix Insertion: A Mechanism to Induce Membrane Fission

“…Membrane fission proceeds through the following steps: membrane neck intermediate, hemifission intermediate, and two separate membrane formation (Corda et al, 2002;Kozlovsky and Kozlov, 2003;Bashkirov et al, 2008;Campelo and Malhotra, 2012;Frolov et al, 2015;Antonny et al, 2016;McDargh and Deserno, 2018;Pannuzzo et al, 2018). Hemifission is an intermediate state where the proximal monolayer (also called contacting monolayer) of the bilayer forming the neck coalesces, thus breaking the inner volume into two parts, while the distal monolayer remains continuous.…”

The role of scaffold reshaping and disassembly in dynamin driven membrane fission

“…However, there is also a second problem: it is by no means obvious how a highly curved bilayer responds to the forces and torques imposed by such complex geometric constraints. Theoretical calculations have provided constraints on energetics and morphology (Kozlov, 1999; Kozlovsky and Kozlov, 2003; Bashkirov et al, 2008; McDargh et al, 2016; McDargh and Deserno, 2018), but these assume high symmetries and ignore fluctuations. Recent coarse-grained (CG) simulations, in which the dynamin helix is represented as a pair of rings, have elucidated the relevance of local torques (Fuhrmans and Müller, 2015) and the possibility of long-lived hemifission intermediates (Mattila et al, 2015; Zhang and Müller, 2017), but the implied mirror symmetry differs from the actual helicoidal one.…”