Diffusion within the cytoplasm: a mesoscale model of interacting macromolecules

Area of Science:

• Biophysics
• Cell Biology
• Computational Biology

Background:

• Cellular cytoplasm's dense environment impacts macromolecule diffusion and organization.
• Physicochemical properties like poly-dispersity and molecular interactions are crucial but not fully understood.
• Previous models often lack detailed consideration of cytoplasmic complexity and specific interactions.

Purpose of the Study:

• To systematically investigate the influence of physicochemical properties on macromolecule diffusion and organization in the bacterial cytoplasm.
• To develop a minimal coarse-grained model of the cytoplasm, including the nucleoid, for simulating biomolecule motion.
• To elucidate the role of intermolecular interactions, including steric repulsion and nonspecific attraction, in modulating transport properties.

Main Methods:

• Stochastic molecular-dynamics simulations of a virtual cytoplasm.
• Tracking single biomolecule motion (3-80 nm) on submillisecond trajectories.
• Combining theoretical approaches with experimental data for model validation.

Main Results:

• Biomolecule diffusion coefficients and anomalous exponents are significantly influenced by intermolecular interactions.
• Models with excluded volume alone show weaker size-dependence than experimental data.
• Incorporating nonspecific attraction (1-10 kT) leads to stronger size-dependent variations in transport properties.
• Normal and anomalous diffusion regimes arise from high concentration, poly-dispersity, stochasticity, and weak interactions.

Conclusions:

• Intermolecular interactions fine-tune the size-dependence of diffusion and viscosity in the cytoplasm.
• Nonspecific attractions play a key role in modulating biomolecule transport.
• Cytoplasmic environment, characterized by poly-dispersity and weak interactions, leads to size-dependent diffusion, with larger molecules experiencing restricted motion due to entanglements and entropic effects.