How the phage T4 injection machinery works including energetics, forces, and dynamic pathway

Area of Science:

• Virology
• Biophysics
• Computational Biology

Background:

• Bacteriophage T4, a Myoviridae family virus, utilizes a contractile sheath for genome injection into Escherichia coli.
• While its atomic structure is known, the dynamic mechanisms of T4's injection machinery remain poorly understood.

Purpose of the Study:

• To develop a system-level model of bacteriophage T4's nonlinear injection machinery dynamics.
• To elucidate the energy mechanisms driving sheath contraction and genome delivery.

Main Methods:

• A continuum model of the contractile sheath was developed using elastic constants from atomistic molecular-dynamics (MD) simulations.
• The sheath model was integrated with component models of the virus and host cell (Escherichia coli).
• System-level simulations captured virus-cell interactions and energy dynamics during injection.

Main Results:

• Simulations identified a
• contraction wave
• propagating along the sheath as the injection pathway.
• The model revealed the energy source powering the injection machinery and forces enabling host cell membrane penetration.
• Energy dissipation mechanisms controlling the injection timescale were also elucidated.

Conclusions:

• The developed system-level model accurately captures bacteriophage T4 injection dynamics.
• The model provides insights into the physical mechanisms of viral genome delivery.
• Results align with limited experimental data, validating the model's predictive capability.