Architecture-encoded mechanics and communication in microtubules: a multiscale computational study

Area of Science:

• Cellular biophysics
• Cytoskeletal dynamics
• Mechanobiology

Background:

• Microtubules (MTs) are essential cytoskeletal components whose mechanical properties influence cellular functions.
• The number of protofilaments (PFs) in MTs varies, but its effect on mechanical signal propagation is poorly understood.
• MT architecture can be adapted based on tubulin composition and cellular environment.

Purpose of the Study:

• To investigate how varying the number of protofilaments (PFs) in microtubules (MTs) affects mechanical signal propagation and structural mechanics.
• To explore the relationship between MT architecture, structural communication, and mechanical properties.

Main Methods:

• Multiscale computational study integrating molecular dynamics, dynamical network analysis, and elastic network modeling.
• Analysis of tubulin-tubulin contact patterns, surface hydrophobicity, and M-loop dynamics.
• Correlation analysis between PF number, vibrational path length, and bending stiffness.

Main Results:

• Increased PF number alters tubulin-tubulin contacts and surface hydrophobicity.
• The dynamics of the M-loop region are modulated by PF number.
• A correlation was found between higher PF numbers, longer vibrational path lengths, and increased bending stiffness.

Conclusions:

• MT architecture, specifically the PF number, influences mechanical signal propagation efficiency and structural support.
• Larger MT architectures transmit mechanical information less efficiently but provide greater stability.
• MT architecture may act as a regulatory mechanism for mechanical signaling and could be relevant to neuromechanobiology.