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Membrane neck formation is essential for scission, which, as recent experiments on tubules have demonstrated, can be location dependent. The diversity of biological machinery that can constrict a neck such as dynamin, actin, ESCRTs and BAR proteins, and the range of forces and deflection over which they operate, suggest that the constriction process is functionally mechanical and robust to changes in biological environment. In this study, we used a mechanical model of the lipid bilayer to systematically investigate the influence of location, symmetry constraints, and helical forces on membrane neck constriction. Simulations from our model demonstrated that the energy barriers associated with constriction of a membrane neck are location-dependent. Importantly, if symmetry restrictions are relaxed, then the energy barrier for constriction is dramatically lowered and the membrane buckles at lower values of forcing parameters. Our simulations also show that constriction due to helical proteins further reduces the energy barrier for neck formation when compared to cylindrical proteins. These studies establish that despite different molecular mechanisms of neck formation in cells, the mechanics of constriction naturally leads to a loss of symmetry that can lower the energy barrier to constriction.
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The role of scaffold reshaping and disassembly in dynamin driven membrane fission
When cells take up material from their surroundings, they must first transport this cargo across their outer membrane, a flexible sheet of tightly organized fat molecules that act as a barrier to the environment. Cells can achieve this by letting their membrane surround the object, pulling it inwards until it is contained in a pouch that bulges into the cell. This bag is then corded up so it splits off from the outer membrane. The ‘cord’ is a protein called dynamin, which is thought to form a tight spiral around the bag’s neck, closing it over and pinching it away. The structure of dynamin is fairly well known, and yet several theories compete to explain how it may snap the bag off the outer membrane. Here, Pannuzzo et al. have created a computer simulation that faithfully replicates the geometry and the elasticity of the membrane and of dynamin, and used it to test different ways the protein could work. The first test featured simple constriction, where the dynamin spiral contracts around the membrane to pinch it; this only separated the bag from the membrane after implausibly tight constriction. The second test added elongation, with the spiral lengthening as well as reducing its diameter, but this further reduced the ability for the protein to snap off the membrane. The final test combined constriction and rotation, whereby dynamin ‘twirls’ as it presses on the neck of the bag: this succeeded in efficiently severing the membrane once the dynamin spiral disassembled. Indeed, the simulations suggested that dynamin might start to dismantle while it constricts, without compromising its role. In fact, getting rid of excess length as the protein contracts helps to dissolve any remnants of a membrane connection. Defects in dynamin are associated with conditions such as centronuclear myopathy and Charcot‐Marie‐Tooth peripheral neuropathy. Recent research also indicates that the protein is involved in a much wider range of neurological disorders that include Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. The models created by Pannuzzo et al. are useful tools to understand how dynamin and similar proteins work and sometimes fail.
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- Award ID(s):
- 1764257
- PAR ID:
- 10104970
- Date Published:
- Journal Name:
- eLife
- Volume:
- 7
- ISSN:
- 2050-084X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.7554/eLife.39441
