Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences

Area of Science:

• Biophysics
• Physical Chemistry
• Biochemistry

Background:

• Macromolecular crowding and confinement are prevalent in biological systems.
• These factors influence macromolecular behavior through volume exclusion and other interactions.
• Understanding these effects is key to comprehending cellular processes.

Purpose of the Study:

• To review the effects of volume exclusion on macromolecular free energy in crowded and confined systems.
• To summarize the impact of crowding and confinement on reaction rates and equilibria.
• To discuss complexities like environmental heterogeneity and non-specific interactions.

Main Methods:

• Review of theoretical, simulation, and experimental literature published since 2004.
• Analysis of findings related to rigid and flexible macromolecules.
• Discussion of approaches to characterize these effects in complex biological media.

Main Results:

• Volume exclusion significantly impacts macromolecular free energy, reaction kinetics, and equilibria.
• Heterogeneity and non-specific interactions add complexity beyond simple steric effects.
• Observed effects align with theoretical predictions in various crowded/confined scenarios.

Conclusions:

• Crowding and confinement are critical determinants of macromolecular behavior in biological environments.
• Further research is needed to fully characterize these effects in systems mimicking living organisms.
• Theoretical and experimental approaches must account for environmental heterogeneity and non-specific interactions.