Estimates of lateral and longitudinal bond energies within the microtubule lattice.
We developed a stochastic model of microtubule (MT) assembly dynamics that estimates tubulin-tubulin bond energies, mechanical energy stored in the lattice dimers, and the size of the tubulin-GTP cap at MT tips. First, a simple assembly/disassembly state model was used to screen possible combinations of lateral bond energy (DeltaG(Lat)) and longitudinal bond energy (DeltaG(Long)) plus the free energy of immobilizing a dimer in the MT lattice (DeltaG(S)) for rates of MT growth and shortening measured experimentally. This analysis predicts DeltaG(Lat) in the range of -3.2 to -5.7 k(B)T and DeltaG(Long) plus DeltaG(S) in the range of -6.8 to -9.4 k(B)T. Based on these estimates, the energy of conformational stress for a single tubulin-GDP dimer in the lattice is 2.1-2.5 k(B)T. Second, we studied how tubulin-GTP cap size fluctuates with different hydrolysis rules and show that a mechanism of directly coupling subunit addition to hydrolysis fails to support MT growth, whereas a finite hydrolysis rate allows growth. By adding rules to mimic the mechanical constraints present at the MT tip, the model generates tubulin-GTP caps similar in size to experimental estimates. Finally, by combining assembly/disassembly and cap dynamics, we generate MT dynamic instability with rates and transition frequencies similar to those measured experimentally. Our model serves as a platform to examine GTP-cap dynamics and allows predictions of how MT-associated proteins and other effectors alter the energetics of MT assembly.
VanBuren
Vincent
V
Department of Biological Sciences, Lehigh University, 111 Research Drive, Bethlehem, PA 18015, USA.
Odde
David J
DJ
Cassimeris
Lynne
L
D019281:Dimerization; D006153:Guanosine Diphosphate / Q000737:chemistry*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D008962:Models, Theoretical; D009010:Monte Carlo Method; D011487:Protein Conformation; D013816:Thermodynamics; D013997:Time Factors; D014404:Tubulin / Q000737:chemistry
D014404:Tubulin; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate