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.

This study demonstrates that the thermally induced collapse of end-grafted poly(N-isopropylacrylamide) (PNIPAM) above the lower critical solution temperature (LCST) of 32 degrees C depends on the chain grafting density and molecular weight. The polymer was grafted from the surface of a self-assembled monolayer containing the initiator (BrC(CH3)2COO(CH2)11S)2, using surface-initiated atom transfer radical polymerization. Varying the reaction time and monomer concentration controlled the molecular weight, and diluting the initiator in the monolayer altered the grafting density. Surface force measurements of the polymer films showed that the chain collapse above the LCST decreases with decreasing grafting density and molecular weight. At T > LCST, the advancing water contact angle increases sharply on PNIPAM films of high molecular weight and grafting density, but the change is less pronounced with films of low-molecular-weight chains at lower densities. Below the LCST, the force-distance profiles exhibit nonideal polymer behavior and suggest that the brush architecture comprises dilute outer chains and much denser chains adjacent to the surface.

The use of liposomes as drug delivery systems has been limited by their rapid clearance from circulation by the mononuclear phagocyte system. Recent studies have found that circulation times can be greatly enhanced by incorporating a small amount of modified lipids whose headgroups are derivatized with a bulky water soluble polymeric chain of poly ethylene oxide. We report here a systematic study using the Surface Forces Apparatus to measure directly the interactions between two phosphatidyl ethanolamine lipid bilayers, exposing this polymeric headgroup at different concentrations in the bilayer. We found that the force becomes repulsive at all separations and that the thickness of the steric barrier could be controlled easily by adjusting the concentration of the modified lipids. Equilibrium force profiles were measured that were reversible and largely insensitive to changes in electrolyte concentration and temperature. The results have enabled the Dolan and Edwards theory for the steric forces of low coverage polymer surfaces and the Alexander de Gennes theory for high coverage surfaces to be tested, and both were found to apply. We conclude that these simple theories can be used to model the interactions of surprisingly short segments and, hence, apply to such systems as lipids with bulky headgroups and liposomes containing a sterically stabilizing polymer.

Vinculin localizes to tension-bearing cell–cell junctions to help transmit signals from E-cadherin to the actin cytoskeleton in response to mechanical stress.

This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields.