Membrane Fusion

Membrane Fusion

One pathway for molecules to enter or exit cells or organelles is through membrane fusion. Thus, membrane fusion plays a key role in many biological processes, including exocytosis, endocytosis, synaptic transmission, fertilization, and viral infection. It has been observed that for lipid bilayers and vesicles to fuse proteins need not always be present to grapple opposing surfaces. Neither is it clear that short-range electrostatic, hydration or steric energies always blockade fusion.

To elucidate alternate mechanisms for membrane fusion, we are investigating thermodynamically favorable pathways where conformational changes between lipid headgroups and tails help them redistribute across the fusing area. For example, such rearrangements may be aided by Calcium or other ions that may collocate with the hydrophilic headgroups. Thus, ionic concentration, pH, and surface electrochemistry may play an important role in understanding membrane fusion.

Similarly, we have shown that water soluble polymers, such as poly(ethylene glycol), can induce fusion by altering the effective phase transition temperature of the constituent lipids. We study fusion between model membranes in real time using the Surface Forces Apparatus (SFA), micropipette aspiration, microscopy, light scattering, and NMR to attain thermodynamic, topological, and chemical descriptors of these mechanisms under a variety of compositional and environmental conditions.

fusion Fusion between membranes is moderated by short-range intermolecular interactions, including hydrophobic forces that: (1) thin the outer leaflet of the lipid bilayer until (2) opposing membranes collapse together, producing (3) hemi-fusion. Like twins joined at the hip, cells unified through hemifusion may be more likely to communicate, share resources, or fuse completely. Interferograms (near left) resolve the membranes’ shapes and separation to ±1Å.

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