OUTLINE OF THE COURSE
(section references are to the book
by Meyer Jackson…see main course page)
Introduction: Course philosophy
Plan, expectations, concerns
Molecular
forces: Section 2.7-2.11
Boltzmann Distribution: Section 1.2
Membrane
structure: time-averaged
Intro on
lipids Section 2.16
What drives self-assembly? Cooperative behavior:
critical micellar concentration
Phospholipid phases: phase transitions
Why dynamic motion? How to
understand it quantitatively.
Lateral motion: measurement, rates: aquaporin
single particle tracking
Flourescence recovery after photobleaching (FRAP): Section 6.10
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?
….cell swelling cell
scanning em
Transient binding of proteins to membranes...quantitative
understanding
Transmembrane potentials
Surface charge...surface potentials...local pH...local pressure
Gouy-Chapman
theory: Section 11.4
Permeation
Diffusion:
Section 6.1, 6.7, 6.8, 6.9
Membrane
Potentials: Sections 13.1-13.5, 13.7
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 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
F-type Na+-ATPase
Baterial flagellum...an ion-driven motor model
Light-coupled proton pumping bacteriorhodopsin bacteriorhodopsin mechanism red lakes
proton conduction
Harvesting energy from light by charge
separation photochemical reaction center photosystem II
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
Insight into the humanity behind the science
Nobel Prize 1997 proton ATPase
Nobel Prize 2003: potassium channel aquaporin