From Thermodynamic States to Biological Function by Einstein's Approach to Statistical Physics

Abstract

Tethers are thin tubes of lipids (~20-200 nm in diameter) that form when membranes are subjected to a point force. Tether dynamics are important to a myriad of biological processes including white blood cell adhesion and transport of intracellular material between neighboring cells. To understand the dynamics of tether formation more fully, we investigated the dependence of the force needed to create a tether on the rate of force change (loading rate). To conduct these experiments, a microfabricated magnetic force transducer was used to generate well-controlled and localized magnetic force profiles. Tethers were formed off the surface of microaspirated giant unilamellar vesicles (GUVs) attached to magnetic beads. We discovered a strong correlation between the threshold force of tether formation and the applied force ramp, with the force changing from <10 pN at low loading rates to~50 pN at high loading rates. At slow loading rates, the threshold force changes weakly with ln (loading rate), while at high loading rates a steeper dependence is observed. The experimental data can be fit to a energetic model based on Kramer's theory, similar to models used to describe membrane rupture. The model predits that tether formation involves passage over two energy barriers and enbales characterization of the characteristic forces and timescales associated with these barriers. This new tool for dynamic studies of membrane mechanics may further be extended to study how tethers form off of flowing cells or how phase regimes, induced by the presence of cholesterol, influence membrane dynamics.

The activity of the intrinsically water-soluble enzyme ADAMTS13 correlates with the membrane state when bound to a phospholipid bilayer

“…An alternative and general explanation for the observed striking correlation of phase transition of the according lipid membrane and enzyme activity is provided by Kaufmann’s theory 41 , 43 as introduced above. This theory is perfectly in line with these and other experimental findings, which observe peaks correlating with the phase transition temperature.…”

“…If one susceptibility exhibits a peak, e.g., the lipid membrane undergoes a melting transition, due to the coupling, all susceptibilities will likely exhibit a peak. As the enzyme is part of the surface and shares a mutual thermodynamic potential, the enzyme activity is another susceptibility and is predicted to display a peak as well 32 , 43 , 46 .…”

Acetylcholinesterase Activity Influenced by Lipid Membrane Area and Surface Acoustic Waves

“…Recently, we have shown that this is also the case for originally water-soluble enzymes when bound to a lipid bilayer [21]. One theory to explain this effect is based on higher fluctuations that occur in the system within a phase transition [22], based on the original theory of Kaufmann [23]. These results make it seem plausible that artificial changes in the membrane environment, such as density modulations, affect the activity of AChE.…”

On the Physical Basis of Biological Signaling by Interface Pulses

“…Kaufmann has developed a theory based on the second law of thermodynamics, according to which changes in catalytic activity represent changes in fluctuation strength of the reaction coordinate induced by the absorption of the substrate 9,10,44 . In another manuscript we indeed demonstrate that the catalytic rate of AChE directly follows the state (compressibility), and 11 hence the fluctuation strength of the interface in which the enzyme is embedded 30,39 .…”