MEMBRANE SHAPING AND REMODELING BY PROTEINS

MEMBRANE SHAPING AND REMODELING BY PROTEINS THANKS AND CREDIT: COLLABORATION: TEL AVIV GROUP: HARVEY MCMAHON ADI PICK TOM RAPOPORT FELIX CAMPELO GUR FABRIKANT WINFRIED WEISSENHORN TOM SHEMESH LEONID CHERNOMORDIK

INTRACELLULAR MEMBRANE SHAPES AND DYNAMICS VIRAL MEMBRANE DYNAMICS Radius of curvature R ~ 20 nm is close to the monolayer thickness h ~4 nm h/R~ 0.2

THREE ESSENTIALLY DIFFERENT GEOMETRICAL TRANSFORMATIONS MEDIATING DYNAMIC SHAPING FISSION FUSION BENDING (GENERATION OF CURVATURE) REMODELING BY FISSION OR FUSION (CHANGE OF MEMBRANE CONTINUITY, AND MEMBRANE TOPOLOGY)

MEMBRANES RESISTS TO BOTH BENDING AND REMODELING MEANING THAT ENERGY HAS TO BE SUPPLIED BY SPECIAL PROTEINS

MEMBRANE RESISTENCE TO MEAN CURVATURE GENERATION: INVOLVED IN SHAPING AND REMODELING BENDING STRESS POSITIVECURVATURE NEGATIVECURVATURE BENDING ENERGY: HELFRICH MODEL BENDING (SPLAY) MODULUS SPONTANEOUS CURVATURE

ENERGY OF GAUSSIAN CURVATURE (HELFRICH MODEL) CHANGE OF MEMBRANE CONNECTIVITY (TOPOLOGY): INVOLVED IN REMODELNG CONSIDERABLE ENERGY IS ASSOCIATED WITH THE FISSION EVENT MODULUS OF GAUSSIAN CURVATURE IN ADDITION, TRANSIENT MEMBRANE DISCONTINUITY REQUIRES ENERGY

QUESTIONS TO ANSWER: PHYSICS: MECHANISTIC PRINCIPLES OF MEMBRANE BENDING AND FUSION/FISSION BY DIFFERENT PROTEINS BASED ON ENERGY CALCULATIONS. BIOLOGY: WHETHER THESE PRINCIPLES ARE UNIVERSAL AND DETERMINE ACTION OF DIVERSE PROTEINS BIOLOGY: WHETHER SAME PROTEINS CAN BE USED TO DRIVE MEMBRANE BENDING AND REMODELING OR DIFFERENT PROTEINS ARE NEEDED BIOLOGY: WHETHER SAME PROTEINS CAN DRIVE BOTH FUSION AND FISSION

CURVATURE GENERATION BY LIPIDS FOR MONOLAYER ASYMMETRICAL STRUCTURE OF LIPID MOLECULES FOR BILAYER EFFICTIVE NON-BILAYER SHAPES OF LIPID MOLECULES ASYMMETRY OF TWO MONOLAYERS: DIFFERENT NUMBERS OF LIPID MOLECULES DIFFERENT LIPID COMPOSITIONS

SPONTANEOUS CURVATURES OF REPRESENTATIVE LIPIDS (RAND AND FULLER) X-rays measurements of lipid mesophases P Rand (Brock Univ., Canada) Lysolipids: Lysophosphatidylcholine (LPC): Common Lipids: Phosphatidylcholine (PC): Hexagonal lipids DioleoylPE (DOPE) Diacylglycerol (DAG)

MECHANISMS OF MEMBRANE CURVATURE GENERATION BY DIRECT ACTION OF PROTEINS HYDROPHOBIC INSERTION SCAFFOLDING CAMPELO ET AL 2008 VOTH ET AL 2008

HYDROPHOBIC-INSERTION MECHANISM OF MEMBRANE BENDING C2 DOMAINS AMPHIPATHIC HELICES N-BAR DOMAINS N-BAR DOMAINS SYNAPTOTAGMIN (D.Z.HERRICK ET AL., 2006) FUSION PEPTIDES SMALL G-PROTEINS L. TAMM, BBA 2007

HYDROPHOBIC INSERTION PROTEINS: EPSIN STRUCTURE MODEL OF ACTION TUBULATION OF PIP2 BILAYERS D=20nm

SCAFFOLDING PROTEINS: BAR DOMAIN PROTEINS STRUCTURE MODEL OF ACTION N-BAR Endophilin BAR TUBULATION OF PS BILAYERS D=20nm

OTHER TYPE OF SCAFFOLDING PROTEINS. EPSIN HOMOLOGY DOMAINS (EHD@) STRUCTURE EHD2 MODEL OF ACTION TUBULATION OF PS BILAYERS TUBULATION IN VIVO BY OVEREXPRESSION D=20nm

SMALL HYDROPHOBIC INSERTION MECHANISM: QUALITATIVELY SMALL INCLUSION GENERATES ELASTIC DEFORMATION OF THE MONOLAYER MATRIX

MEMBRANE AS A THICK LAYER: RELEVANT SCALES ARE COMPARABLE WITH MEMBRANE THICKNESS INTRA-MEMBRANE DISTRIBUTION OF STRESSES AND RIGITIES TRANS-MEMBRANE STRESS PROFILE from Illya, Lipowsky and Shillcock, J Chem Phys 122, 244901 (2005) σ

TRANS-MEMBRANE ELASTICITY PROFILE STRETCHING TRANSVERSE SHEAR λT λS λT λS λ

COMPUTING MEMBRANE BENDING BY INSERTIONS FELIX CAMPELO BEFORE INSERTION DEFORMED STATE AFTER INSERTION LOOKING FOR CONFORMATION OF MINIMAL ELASTIC ENERGY

EFFECTIVE SPONTANEOUS CURVATURE OF INSERTION MAXIMAL SPONT.CURV. FOR INCLUSION MAXIMAL SPONT.CURV. FOR LIPID (LPC) ζLPCh ~ 0.3 ζinch ~ 0.75 EFFECTIVE SPONTANEOUS CURVATURE OF INSERTION Zinc/h

MEMBRANE TUBULATION BY N-BAR DOMAIN 0.05 zinch

SHALLOW HYDROPHOBIC INSERTIONS ARE MORE EFFECTIVE THEN LIPIDS IN CURVATURE GENERATION

CURVATURE GENERATION BY SCAFFOLDING PROTEINS: SHAPING OF ENDOPLASMIC RETICULUM

MEMBRANE SHAPING AND REMODELING BY PROTEINS