Microtubule instability driven by longitudinal and lateral strain propagation

Area of Science:

• Biophysics
• Cell Biology
• Structural Biology

Background:

• Microtubules (MTs) are dynamic polymers essential for cell structure and function.
• MT stability is regulated by GTP hydrolysis within tubulin dimers.
• The precise energetic and dynamic consequences of GTP hydrolysis on the MT lattice remain incompletely understood.

Purpose of the Study:

• To investigate the impact of GTP hydrolysis on tubulin lattice conformation, lateral interactions, and dimer dynamics.
• To elucidate the mechanisms by which GTP hydrolysis destabilizes the microtubule lattice.

Main Methods:

• Long-time atomistic molecular dynamics simulations were employed.
• Analysis focused on lattice energetics, strain, lateral inter-dimer interactions, and dimer motion coordination.

Main Results:

• GTP hydrolysis energy is primarily stored as longitudinal strain within the tubulin lattice.
• Lateral bond stability is minimally affected by GTP hydrolysis.
• Stored elastic energy leads to confined and correlated dynamics of GDP-tubulin dimers, increasing lattice entropy.

Conclusions:

• Longitudinal strain and altered GDP-tubulin dynamics are key consequences of GTP hydrolysis.
• These changes entropically destabilize the microtubule lattice, promoting disassembly.
• The findings provide a detailed mechanistic understanding of microtubule dynamics and instability.