Abstract
Membrane fusion is critical to biological processes such as viral infection, endocrine hormone secretion, and neurotransmission, yet the precise mechanistic details of the fusion process remain unknown. Current experimental and computational model systems approximate the complex physiological membrane environment for fusion using one or a few protein and lipid species. Here, we report results of a computational model system for fusion in which the ratio of lipid components was systematically varied, using thousands of simulations of up to a microsecond in length to predict the effects of lipid composition on both fusion kinetics and mechanism. In our simulations, increased phosphatidylcholine content in vesicles causes increased activation energies for formation of the initial stalk-like intermediate for fusion and of hemifusion intermediates, in accordance with previous continuum-mechanics theoretical treatments. We also use our large simulation dataset to quantitatively compare the mechanism by which vesicles fuse at different lipid compositions, showing a significant difference in fusion kinetics and mechanism at different compositions simulated. As physiological membranes have different compositions in the inner and outer leaflets, we examine the effect of such asymmetry, as well as the effect of membrane curvature on fusion. These predicted effects of lipid composition on fusion mechanism both underscore the way in which experimental model system construction may affect the observed mechanism of fusion and illustrate a potential mechanism for cellular regulation of the fusion process by altering membrane composition.
Highlights
Membrane fusion plays a key role in cellular function, allowing processes as diverse as neurotransmitter release, secretion of peptide hormones, and infection by enveloped viruses
Membrane fusion is the transport process used for neurotransmitter release, insulin secretion, and infection by enveloped viruses
We present initial results on fusion of vesicles at different membrane curvatures
Summary
Membrane fusion plays a key role in cellular function, allowing processes as diverse as neurotransmitter release, secretion of peptide hormones, and infection by enveloped viruses. A variety of experimental and computational model systems [5,6,7,8,9,10,11,12,13,14] have been used to gain insight into the basic physical properties underlying membrane fusion. Such model systems are of necessity much simpler in nature than the physiologic context for fusion, containing one or a few lipid species and omitting or simplifying the protein environment. Investigating how changes in lipid composition affect the kinetics and mechanism of fusion provides fundamental insight by illuminating which aspects of fusion are robust to small perturbations to the model system used and which are highly model-dependent
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
