Results from a fieldtheoretic approach to membrane fusion

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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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(No Transcript)
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Synaptic Vesicles
They are small R15-25 nm cf bilayer thickness
t4nm 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-gtRandom walk-gtDiffusion
Eq.-gt Quantum Mech.
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Theoretical Procedure
Consider fusion of vesicles of block copolymer
universality Polymers-gtRandom walk-gtDiffusion
Eq.-gt Quantum Mech. SCFT of interacting
polymers-gt Hartree Theory Advantages microscopic
model-gtarchitecture
calculation of free energies
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WHY DOES FUSION OCCUR?
Bringing bilayers together removes water-gt free
energy per area increases-gt bilayers are under
tension
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WHY DOES FUSION OCCUR?
Bringing bilayers together removes water-gt free
energy per area increases-gt bilayers are under
tension
Fusion eliminates area -gt reduces the free
energy Fusion is one possible response to
induced tension Lysis (rupture) is another
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HOW DOES FUSION OCCUR?

• one commonly accepted mechanism

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Profiles obtained by the theory
Kozlov and Markin 1983
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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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Profiles obtained by the theory
Kozlov and Markin 1983
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1 bilayer 4.3 Rg
One component, f 0.4 (DOPC), g/g0 0.2,
equilibrium H, stalk
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One component, f 0.4, g/g0 0.2, equilibrium
H, stalk
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One component, f 0.4, g/g0 0.2, equilibrium
H, stalk
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One component, f 0.4, g/g0 0.2, equilibrium
H, stalk
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One component, f 0.4, g/g0 0.2, equilibrium
H, pore
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One component, f 0.4, g/g0 0.2, equilibrium
H, stalk pore
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In lipids, barrier would be 50 kT !
One component, f 0.4, g/g0 0.2, equilibrium
H, stalk pore
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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
F/kbT
0.40 in cis
0.43 in cis
f0.4 (DOPC) and f0.294 (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
F/kbT
0.40 in cis
Note that stalk becomes metastable. Its
formation is now largest barrier
0.43 in cis
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Effect of curvatureFusion of Bilayer and
Vesicle
1 bilayer 4.3 Rg
6040 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
6040 mixture
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Control Fusion by Controlling the Interbilayer

Spacing
H 2.2 R_g, zero tension, 6040 mixture
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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
  -gteasy to prevent fusion

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Conclusions

• Two barriers to fusion
• Barrier to stalk formation linear in distance
  -gteasy 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
  -gteasy 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 Mueller Kirill Katsov Jae-Youn Lee NSF
Grant DMR 0503752