440 likes | 536 Views
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
E N D
Results from a field-theoreticapproach to membrane fusion Michael Schick Department of Physics University of Washington
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
WHY DOES FUSION OCCUR? 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
HOW DOES FUSION OCCUR? one commonly accepted mechanism
Profiles obtained by the theory Kozlov and Markin 1983
WHAT ARE THE FREE ENERGY BARRIERS TO FUSION? Consider the fusion of two bilayers One component only A lamellar former
Profiles obtained by the theory Kozlov and Markin 1983
1 bilayer =4.3 Rg One component, f = 0.4 (DOPC), g/g0 = 0.2, equilibrium H, stalk
One component, f = 0.4, g/g0 = 0.2, equilibrium H, stalk & pore
In lipids, barrier would be 50 kT ! One component, f = 0.4, g/g0 = 0.2, equilibrium H, stalk & pore
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 F/kbT 0.40 in cis 0.43 in cis 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 F/kbT 0.40 in cis Note that stalk becomes metastable. Its formation is now largest barrier 0.43 in cis
Effect of curvatureFusion of Bilayer and Vesicle: 1 bilayer =4.3 Rg 60:40 mixture J Y Lee & M.S. BJ 2008
As vesicle radius decreases, effective tension increases, which decreases barrier
Fusion of two identical vesicles 60:40 mixture
Control Fusion by Controlling the Interbilayer Spacing H = 2.2 R_g, zero tension, 60:40 mixture
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 Mueller Kirill Katsov Jae-Youn Lee NSF Grant DMR 0503752