results from a field-theoretic approach to membrane fusion
DESCRIPTION
Results from a field-theoretic approach to membrane fusion. Michael Schick Department of Physics University of Washington. à mon cher maître. à mon cher maître. à mon cher maître. Maurice Ravel. Synaptic Vesicles. They are small R~15-25 nm cf bilayer thickness t~4nm - PowerPoint PPT PresentationTRANSCRIPT
Results from a field-theoreticapproach to membrane fusion
Michael Schick
Department of Physics
University of Washington
à mon cher maître
à mon cher maître
à mon cher maître
Maurice Ravel
Synaptic Vesicles
They are small R~15-25 nm
cf bilayer thickness t~4nm
They dock: nothing happens
They are triggered: fuse rapidly
Fusion on demand
Synaptic vesicles in C. Elegans
J.L. Bessereau: www.biologie.ens.fr
Questions
• Why does fusion occur and how?
• What are free energy barriers to fusion?
• What factors promote fusion?
Theoretical Procedure
Consider fusion of vesicles of block copolymer: universality
Theoretical Procedure
Consider fusion of vesicles of block copolymer: universality
Polymers->Random walk->Diffusion Eq.-> Quantum Mech.
Theoretical Procedure
Consider fusion of vesicles of block copolymer: universality
Polymers->Random walk->Diffusion Eq.-> Quantum Mech.
SCFT of interacting polymers-> Hartree Theory
Advantages: microscopic model->architecture
calculation of free energies
Bringing bilayers together removes water->
free energy per area increases-> bilayers are under tension
WHY DOES FUSION OCCUR?
Bringing bilayers together removes water->
free energy per area increases-> bilayers are under tension
Fusion eliminates area -> reduces the free energy
Fusion is one possible response to induced tension
Lysis (rupture) is another
WHY DOES FUSION OCCUR?
HOW DOES FUSION OCCUR?
one commonly accepted mechanism
Kozlov and Markin 1983
Profiles obtained by the theory
WHAT ARE THE FREE ENERGY BARRIERS TO FUSION?
WHAT ARE THE FREE ENERGY BARRIERS TO FUSION?
Consider the fusion of two bilayers
One component only
A lamellar former
Kozlov and Markin 1983
Profiles obtained by the theory
One component, f = 0.4 (DOPC), /0 = 0.2, equilibrium H, stalk
1 bilayer =4.3 Rg
One component, f = 0.4, /0 = 0.2, equilibrium H, stalk
One component, f = 0.4, /0 = 0.2, equilibrium H, stalk
One component, f = 0.4, /0 = 0.2, equilibrium H, stalk
One component, f = 0.4, /0 = 0.2, equilibrium H, pore
One component, f = 0.4, /0 = 0.2, equilibrium H, stalk & pore
One component, f = 0.4, /0 = 0.2, equilibrium H, stalk & pore
In lipids, barrier would be 50 kT !
WHAT FACTORS AFFECT FUSION?
Effect of Tension
Effect of Two Components and Asymmetry in Leaves
SMALL HEADS, LARGE TAILS FAVORED HERE IN PROXIMAL LEAF
Effect of Two Components and Asymmetry in Leaves
Average concentration of hex-former is 0.35
0.35 in cis
0.40 in cis
0.43 in cis
F/kbT
f=0.4 (DOPC) and f=0.294 (DOPE)
Effect of Two Components and Asymmetry in Leaves
Average concentration of hex-former is 0.35
0.35 in cis
0.40 in cis
0.43 in cis
F/kbT
Note that stalk becomes metastable. Its formation is now largest barrier
Effect of curvatureFusion of Bilayer and Vesicle:
1 bilayer =4.3 Rg60:40 mixture J Y Lee & M.S. BJ 2008
What should we expect the effect of curvature to be?
As vesicle radius decreases, effective tension increases, which decreases barrier
Fusion of two identical vesicles
60:40 mixture
H = 2.2 R_g, zero tension, 60:40 mixture
Control Fusion by Controlling the Interbilayer Spacing
H = 2.2, 2.7 R_g, zero tension
H = 2.2, 2.7, 3.2 R_g, zero tension
H = 2.2, 2.7, 3.2, 3.7 R_g, zero tension
H = 2.2, 2.7, 3.2, 3.7, 4.0 R_g, zero tension
Conclusions• Two barriers to fusion
Conclusions• Two barriers to fusion• Barrier to stalk formation linear in distance
->easy to prevent fusion
Conclusions• Two barriers to fusion• Barrier to stalk formation linear in distance
->easy to prevent fusion• Second barrier reduced by composition and
curvature
Conclusions• Two barriers to fusion• Barrier to stalk formation linear in distance
->easy to prevent fusion• Second barrier reduced by composition and
curvature• Consequently, when brought close, stalk
barrier is small, ~13kT, and fusion is quick• Fusion on demand!
Acknowledgements
Marcus MuellerKirill KatsovJae-Youn Lee
NSF Grant DMR 0503752