OUTLINE OF THE COURSE

 

Introduction:  Course philosophy
                        Plan, expectations, concerns

Membrane structure:   time-averaged  Intro on lipids

Membranes do not stretch: cell swelling cell scanning EM

Membrane curvature: ceramide-induced budding

What drives self-assembly?  Cooperative behavior: critical micellar concentration
Phospholipid phases: phase transitions 
Why dynamic motion? What motions take place?
Lateral motion: measurement, rates: aquaporin   single particle tracking lateral diffusion movies

Lateral phase separation in liposomes: paper1 paper2

Flourescence recovery after photobleaching (FRAP) you tube movie
Visualization using molecular simulation:
  membrane simulations 
Stability of structure of membrane components: energy level, hydropathy scales 

hydropathy scales paper  VDAC images
What determines spacing between phospholipids? What determines membrane thickness?

Transient binding of proteins to membranes...quantitative understanding
Transmembrane potentials
Surface charge...surface potentials...local pH...local pressure

Gouy-Chapman theory

Permeation

Diffusion experimental results

Membrane Potentials

Barriers to permeation....building small compartments
Solubility-diffusion vs. molecular sieving  permeability data
The influence of charge: why are larger structures more permeable through membranes?  Born
Dipole Potential  
Flux Equations    energetics 

Equilibrium situations: electrostatic, osmotic 
Origins of membrane potentials
Mechanisms of enhanced permeation  membrane transport

Carrier-based Translocation 

Fundamental processes: symport, antiport, uniport   mitochondrial transport
Energy transduction using carriers: energy conservation, energy distribution, efficiency vs. rate of output
 
Glusose transport systems   review of glucose transport  glucose transport

Structure and function of ATP/ADP translocator (antiport)

Ion pumps

The smallest, most abundant motor on the planet.  H+-ATPase ATP synthase
       Fo mechanism ATP synthase PDB site

Achieving energy transduction between ion gradients and ATP
Movies: 12345 YouTube movie YouTube movie YouTube movie YouTube movie
Rotation movies

F-type Na+-ATPase ATP synthase structures

Atomic force microscopy of ATPase dynamics
Baterial flagellum...an ion-driven motor model

Light-coupled proton pumping  bacteriorhodopsin bacteriorhodopsin mechanism red lakes proton conduction
YouTube movie YouTube movie YouTube movie

Harvesting energy from light by charge separation   photochemical reaction center  photosystem II YouTube movie
Redox-driven proton pumping: citric acid cycle electron transport chain redox potential

electron transport chain  electron transport chain  oxidative phosphorylation 

  cytochrome oxidase mechanism
 complex I  complex I  complex I power point   complex III (b-c1 complex)
Ca-ATPase  mechanism figures:123 

Coupled flow: fig1 fig2 paper get page 1897


Channels

simple overview 12 compendium of ion channels
Experimental measurements
Formation by toxins: agents for chemical warfare among micro-organisms gramicidin gramicidin simulation
Known structures: complex machines with subtle beauty    maltoporin  maltoporin movie  MscL   KcsA KcsA-Roux  channels etc.  
Gating processes: detecting and responding to environmental stimuli
   models of gating (from Ion Channels of Excitable Membranes by Hille)

Analysis of voltage gating  theory   I/V plots
Force felt by the protein; gating current

Voltage gated channels
 Power point presentations:   blocking and selectivity  

Eisenman sequences

VDAC Na+-K+-Ca++ channels Hodgkin/Huxley action potential simulation

Papers on KcsA 1 2 3

Experimental approaches to channel gating: Biotin/Avidin

Ion Selectivity an extreme example PorA/C1

Achieving high flow and high selectivity: well-designed channels are far more than just holes

Access resistance: getting there can be half the battle

 

Complex membrane phenomena

oxidative phosphorylation chemiosmotic coupling

action potential generation...Hodgkin-Huxley model equations

Background

Protein Structure

Insight into the humanity behind the science

Hodgkin and Huxley

Peter Mitchell

Nobel Prize 1988 photosynthetic reaction center

Nobel Prize 1997 proton ATPase

Nobel Prize 2003: potassium channel aquaporin

other