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

Flourescence recovery after photobleaching (FRAP) 
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
       Fo mechanism

      Yoshida
Achieving energy transduction between ion gradients and ATP
Movies: 12345 YouTube movie YouTube movie YouTube movie YouTube movie
F-type Na+-ATPase   ATP synthase structures
Baterial flagellum...an ion-driven motor  model
YouTube movie
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: electron transport chain  electron transport chain   oxidative phosphorylation  cytochrome oxidase  cytochrome oxidase mechanism
 complex I  complex I   complex I power point    complex III (b-c1 complex)
Ca-ATPase 0.26 nm crystal structure  see mechanism in text  Ca-ATPase figures:123  Ca-ATPase


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.  
ryanodine receptor 
 
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
Papers on KcsA   1   2   3  

Experimental approaches to channel gating:    Biotin/Avidin
Ion Selectivity (T: p 10-11)   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