Actin is fundamental to cell function. It is a protein occurring in all eukaroytic cells, varying little in amino acid sequence from species to species. Globular actin (G-actin) consists of 375 amino acid residues and has a molecular weight of 42,000. Filamentary actin (F-actin) is a polymeric form of G-actin, and is a double-stranded right-hand helix. The polymerization of G-actin to F-actin occurs under particular conditions of temperature, pressure, G-actin concentration, the concentrations of salts, ATP and/or ADP, etc. This polymerization from G- to F-actin is crucial to how cells hold their structure, and to how they move from place to place. The mechanism for this polymerization is not understood. In order to understand the polymerization of actin, we need to understand the thermodynamics of the process. The thermodynamic information in the literature is contradictory and incomplete. Our first goal is to make accurate measurements of important properties during the course of the polymerization: the mass density by dilatometry, the enthalpy by stopped flow calorimetry, the extent of polymerization by fluorescence spectrometry, and the concentration susceptibility and length scales by neutron scattering, all as functions of the several variables listed above. This information alone will give important insight into the polymerization mechanism, such as whether the volume increases or decreases, and how the heat of polymerization depends on salt concentration. Our second goal is to test the hypothesis that the polymerization of actin can be described by the same statistical mechanical models used for other second order phase transitions and other polymerizations. We will test the hypothesis by comparing the theory to the measurements discussed above. If the hypothesis holds, then (1) the mathematical framework for making calculations for actin exists and is available for use, and (2) any mechanism proposed for actin must satisfy the thermodynamics of second order phase transitions.
| Matthews, Jermey N A; Yim, Peter B; Jacobs, Donald T et al. (2005) The polymerization of actin: extent of polymerization under pressure, volume change of polymerization, and relaxation after temperature jumps. J Chem Phys 123:074904 |
