Biomedical Engineering Reference
In-Depth Information
The Current Challenge
Pierre Bongrand
CONTENTS
1.1
Introduction....................................................................................................... 2
1.2
What Is the Use of Biomolecular Interactions? ................................................ 3
1.2.1
Cell Structure: Statics and Dynamics................................................... 3
1.2.2
Cell Differentiation............................................................................... 4
1.2.3
Cell Adhesion ....................................................................................... 4
1.2.4
Immune Recognition ............................................................................ 7
1.2.5
Signal Generation ................................................................................. 8
1.3
Brief Historical Outline of Recent Investigations Made on Biomolecule
Recognition at the Single Bond Level .............................................................. 9
1.3.1
Studying Bond Rupture at the Single Molecule Level....................... 10
1.3.2
Measuring Bond Formation at the Single Molecule Level ................ 13
1.4
Which Parameters Do We Need to Account for Biomolecule
Recognition? ................................................................................................... 15
1.4.1
The Affinity Constant ......................................................................... 16
1.4.2
Kinetic Constants: The On-Rate and the Off-Rate............................. 17
1.4.2.1
The Force-Dependent Dissociation Rates .......................... 17
1.4.2.2
Distance-Dependent Association Rates ............................. 19
1.4.3
Avidity of Biomolecule Interactions: An Incompletely Defined
Parameter............................................................................................ 21
1.4.4
Specificity of Biomolecule Interactions: An Essential Property
That Is Difficult to Define Accurately ................................................ 22
1.4.5
Ligand-Receptor Interactions Are Influenced by Parameters
That Are Extrinsic to Both Ligand and Receptor Molecules ............. 23
1.5
Relationship between Biomolecule Structure and Recognition Events ......... 24
1.5.1
Intermolecular Forces in the Biological Milieu ................................. 25
1.5.1.1
Electrostatic Forces ............................................................ 25
1.5.1.2
The Hydrogen Bond ........................................................... 26
1.5.1.3
Different Timescale: Electrodynamic Interactions............. 27
1.5.1.4
Using the Formalism of Surface Physical-Chemistry:
Hydrophobic Bonds............................................................ 28
1.5.2
General Properties of Ligand-Receptor Association ......................... 30
1.5.2.1
A Static View of Ligand-Receptor Complexes.................. 30
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