Abstract:
:The pathway to membrane fusion in synthetic and biological systems is thought to pass through hemifusion, in which the outer leaflets are fused while the inner leaflets engage in a hemifusion diaphragm (HD). Fusion has been proposed to be completed by lysis of the expanded HD that matures from a localized stalklike initial connection. However, the process that establishes the expanded HD is poorly understood. Here we mathematically modeled hemifusion of synthetic vesicles, where hemifusion and fusion are most commonly driven by calcium and membrane tension. The model shows that evolution of the hemifused state is driven by these agents and resisted by interleaflet frictional and tensile stresses. Predicted HD growth rates depend on tension and salt concentration, and agree quantitatively with experimental measurements. For typical conditions, we predict that HDs expand at ~30 μm(2)/s, reaching a final equilibrium area ~7% of the vesicle area. Key model outputs are the evolving HD tension and area during the growth transient, properties that may determine whether HD lysis occurs. Applying the model to numerous published experimental studies that reported fusion, our results are consistent with a final fusion step in which the HD ruptures due to super-lysis HD membrane tensions.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Warner JM,O'Shaughnessy Bdoi
10.1016/j.bpj.2012.06.041subject
Has Abstractpub_date
2012-08-22 00:00:00pages
689-701issue
4eissn
0006-3495issn
1542-0086pii
S0006-3495(12)00730-8journal_volume
103pub_type
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