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DNA:
A programmable Force Sensor
Hauke Clausen-Schaumann et al. 2003
To directly quantify biomolecular interaction
General Goal:
Why?
“…it has become evident that bimolecular processes aregoverned by piconewton forces”
• Receptor-ligand interactions
•Protein and nucleic acid structures
•Covalent bonds
Examples:
The next goal:
To detect single-base pair mismatch using Single-molecular forces measurements
***Previous best was 10 base pairs***
Previous best method used Atomic Force Microscopy
AFM
or
The cantilever spring method:
Glass slide
Rudder stamp
The new method (differential force) :
Glass slide
Rudder stamp
The single-base pair mismatchchallenge:
PM > MM
Cy5 intensity = strength
Shear Geometry vs.
Zip Geometry
Have :
•Identical sequence•Binding energies•Thermal on/off rates
…but the zip 25-mer is 15 fold
more likely to rupture!
The Application:
A means of discriminating betweenspecific and non-specificantibody antigen interactions
Cy3 intensity = strength
False Positive detection:
• Protein array confirmation
• Since false positives increase geometrically as the number of spots increases.
• Could increase specificity
Questions:
1. Data is presented as intensity (probabilities), not forces
2. How complex are the mechanics of the tug-of-war?
3. How useful would it really be for “Precision SNP detection”?
4. Applications for DNA arrays
5. Chip design cost?
6. Cost of synthesizing antibodies couples to oligos on the rubber stamp thing?