0. Abbreviations 1061. Introduction: overview of forces in biology 1081.1 Subtleties of biological forces and interactions 1081.2 Specific and non-specific forces and interactions 1131.3 van der Waals (VDW) forces 1141.4 Electrostatic and ’double-layer‘ forces (DLVO theory) 1221.4.1 Electrostatic and double-layer interactions at very small separation 1261.5 Hydration and hydrophobic forces (structural forces in water) 1311.6 Steric, bridging and depletion forces (polymer-mediated and tethering forces) 1371.7 Thermal fluctuation forces: entropic protrusion and undulation forces 1421.8 Comparison of the magnitudes of the major non-specific forces 1461.9 Bio-recognition 1461.10 Equilibrium and non-equilibrium forces and interactions 1501.10.1 Multiple bonds in parallel 1531.10.2 Multiple bonds in series 1552. Experimental techniques for measuring forces between biological molecules and surfaces 1562.1 Different force-measuring techniques 1562.2 Measuring forces between surfaces 1612.3 Measuring force–distance functions, F(D) 1612.4 Relating the forces between different geometries: the ‘Derjaguin Approximation’ 1622.5 Adhesion forces and energies 1642.5.1 An example of the application of adhesion mechanics of biological adhesion 1662.6 Measuring forces between macroscopic surfaces: the surface forces apparatus (SFA) 1672.7 The atomic force microscope (AFM) and microfiber cantilever (MC) techniques 1732.8 Micropipette aspiration (MPA) and the bioforce probe (BFP) 1772.9 Osmotic stress (OS) and osmotic pressure (OP) techniques 1792.10 Optical trapping and the optical tweezers (OT) 1812.11 Other optical microscopy techniques: TIRM and RICM 1842.12 Shear flow detachment (SFD) measurements 1872.13 Cell locomotion on elastically deformable substrates 1893. Measurements of equilibrium (time-independent) interactions 1913.1 Long-range VDW and electrostatic forces (the two DVLO forces) between biosurfaces 1913.2 Repulsive short-range steric–hydration forces 1973.3 Adhesion forces due to VDW forces and electrostatic complementarity 2003.4 Attractive forces between surfaces due to hydrophobic interactions: membrane adhesion and fusion 2093.4.1 Hydrophobic interactions at the nano- and sub-molecular levels 2113.4.2 Hydrophobic interactions and membrane fusion 2123.5 Attractive depletion forces 2133.6 Solvation (hydration) forces in water: forces associated with water structure 2153.7 Forces between ‘soft-supported’ membranes and proteins 2183.8 Equilibrium energies between biological surfaces 2194. Non-equilibrium and time-dependent interactions: sequential events that evolve in space and time 2214.1 Equilibrium and non-equilibrium time-dependent interactions 2214.2 Adhesion energy hysteresis 2234.3 Dynamic forces between biomolecules and biomolecular aggregates 2264.3.1 Strengths of isolated, noncovalent bonds 2274.3.2 The strengths of isolated bonds depend on the activation energy for unbinding 2294.4 Simulations of forced chemical transformations 2324.5 Forced extensions of biological macromolecules 2354.6 Force-induced versus thermally induced chemical transformations 2394.7 The rupture of bonds in series and in parallel 2424.7.1 Bonds in series 2424.7.2 Bonds in parallel 2444.8 Dynamic interactions between membrane surfaces 2464.8.1 Lateral mobility on membrane surfaces 2464.8.2 Intersurface forces depend on the rate of approach and separation 2494.9 Concluding remarks 2535. Acknowledgements 2556. References 255While the intermolecular forces between biological molecules are no different from those that
arise between any other types of molecules, a ‘biological interaction’ is usually very different
from a simple chemical reaction or physical change of a system. This is due in part to the
higher complexity of biological macromolecules and systems that typically exhibit a hierarchy
of self-assembling structures ranging in size from proteins to membranes and cells, to tissues
and organs, and finally to whole organisms. Moreover, interactions do not occur in a linear,
stepwise fashion, but involve competing interactions, branching pathways, feedback loops,
and regulatory mechanisms.
