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Lipid Nanodisc Sligar 2002 (Motivation (Structure + Dynamics (Different…

- - - - Length (Usual length is in the range of 14:18)
      - Charge and polarity of the head group
      - Saturation
    - - :fire: Symmetry: Is it possible to make an unsymmetrical ND?
      - Curvature depends on the lipid packing
        Tieleman 2015
      - Lipid mix and cholesterol
  - - - Length can be engineered by insertion of additional amphipathic helices in the central part of MSP (7-12 nm in diameter)
      - human apolipoprotein A-1, natural scaffold of HDL
        Riek 2017
      - covalently circularized MSP
        Wagner 2016
        
        :check: suitable for bigger membrane complexes
        up to 80nm in diameter
        
        :check: improved thermal stability
        
        :red_cross: Less biologically relevant. Might introduce additional strains
      - :fire: pH: Is it possible to enlarge the pH range amenable to the ND?
    - - SMALPs
        Garavito 2001
      - Considerations
        
        :check: smaller mass
        
        \( R_2 = \overline{\omega^2(t)} \tau_c \)
        
        \( \Delta \omega_{FWHH} \ \ \ \ = 2R_2 \)
        
        \( \tau_c = 4\pi\eta_Wr^3_H/(3k_BT) \)
        
        Line width \( \propto \) MW
        
        :check: detergent free extraction
        
        :red_cross: single lipid layer does not exploit full ND advantage of being membrane mimicking structure
- - - - Tissue factors (TFs)
        Sligar 2007
      - Bacteriorhodopsin (bR)
        Sligar 2003
      - KcsA
        Shenkarev 2009
        
        How the potassium binding potency is affected by ND embedding? :fire:
        
        TROSY spectra of closed chanel :fire:
    - - GPCRs
        Sligar 2006
      - Chemoreceptors
        Hazelbauer 2006
      - Peptide translocon
        Dalal 2009
      - Tyrosine kinases
        Springer 2008
- - - - MAS SSNMR was performed on nanodisc-embedded Human Cytochrome P450
        Sligar 2007
      - liquid NMR
        Shenkarev 2009
        
        :red_cross: Biggest problem:
        High Molecular Weight
        
        Increase sensitivity via various
        polarization transfer techniques :fire:
        
        Ligand detection
        
        More scans, more temperature, more concentration,
        100% deturation, water suppression etc.