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
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Results from a field-theoreticapproach to membrane fusion
Michael Schick
Department of Physics
University of Washington
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à mon cher maître
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à mon cher maître
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à mon cher maître
Maurice Ravel
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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
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Synaptic vesicles in C. Elegans
J.L. Bessereau: www.biologie.ens.fr
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Questions
• Why does fusion occur and how?
• What are free energy barriers to fusion?
• What factors promote fusion?
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Theoretical Procedure
Consider fusion of vesicles of block copolymer: universality
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Theoretical Procedure
Consider fusion of vesicles of block copolymer: universality
Polymers->Random walk->Diffusion Eq.-> Quantum Mech.
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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
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Bringing bilayers together removes water->
free energy per area increases-> bilayers are under tension
WHY DOES FUSION OCCUR?
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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?
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HOW DOES FUSION OCCUR?
one commonly accepted mechanism
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Kozlov and Markin 1983
Profiles obtained by the theory
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WHAT ARE THE FREE ENERGY BARRIERS TO FUSION?
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WHAT ARE THE FREE ENERGY BARRIERS TO FUSION?
Consider the fusion of two bilayers
One component only
A lamellar former
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Kozlov and Markin 1983
Profiles obtained by the theory
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One component, f = 0.4 (DOPC), /0 = 0.2, equilibrium H, stalk
1 bilayer =4.3 Rg
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One component, f = 0.4, /0 = 0.2, equilibrium H, stalk
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One component, f = 0.4, /0 = 0.2, equilibrium H, stalk
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One component, f = 0.4, /0 = 0.2, equilibrium H, stalk
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One component, f = 0.4, /0 = 0.2, equilibrium H, pore
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One component, f = 0.4, /0 = 0.2, equilibrium H, stalk & pore
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One component, f = 0.4, /0 = 0.2, equilibrium H, stalk & pore
In lipids, barrier would be 50 kT !
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WHAT FACTORS AFFECT FUSION?
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Effect of Tension
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Effect of Two Components and Asymmetry in Leaves
SMALL HEADS, LARGE TAILS FAVORED HERE IN PROXIMAL LEAF
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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)
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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
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Effect of curvatureFusion of Bilayer and Vesicle:
1 bilayer =4.3 Rg60:40 mixture J Y Lee & M.S. BJ 2008
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What should we expect the effect of curvature to be?
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As vesicle radius decreases, effective tension increases, which decreases barrier
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Fusion of two identical vesicles
60:40 mixture
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H = 2.2 R_g, zero tension, 60:40 mixture
Control Fusion by Controlling the Interbilayer Spacing
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H = 2.2, 2.7 R_g, zero tension
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H = 2.2, 2.7, 3.2 R_g, zero tension
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H = 2.2, 2.7, 3.2, 3.7 R_g, zero tension
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H = 2.2, 2.7, 3.2, 3.7, 4.0 R_g, zero tension
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Conclusions• Two barriers to fusion
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Conclusions• Two barriers to fusion• Barrier to stalk formation linear in distance
->easy to prevent fusion
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Conclusions• Two barriers to fusion• Barrier to stalk formation linear in distance
->easy to prevent fusion• Second barrier reduced by composition and
curvature
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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!
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Acknowledgements
Marcus MuellerKirill KatsovJae-Youn Lee
NSF Grant DMR 0503752