Macromolecular crowding and confinement in cells exposed to hypertonicity

Area of Science:

• Biophysics
• Cell Biology
• Biochemistry

Background:

• High concentrations of macromolecules in solutions exhibit nonideal properties, increasing macromolecular activity.
• Molecular crowding and confinement are proposed intracellular phenomena influencing protein and macromolecule activity.
• These effects have significant implications for cell volume regulation due to concentration changes altering macromolecular activity.

Purpose of the Study:

• To review the physical chemical principles of macromolecular crowding and confinement.
• To examine in vitro demonstrations and the relationship to water activity.
• To assess the role of crowding in osmotic regulation across various cell types.

Main Methods:

• Review of physical chemical principles governing macromolecular interactions.
• Analysis of in vitro experimental data demonstrating crowding effects.
• Examination of intracellular water and macromolecule activity estimates.
• Integration of data on osmotic regulation in bacteria, red blood cells, and complex nucleated cells.

Main Results:

• Compelling evidence supports significant effects of molecular crowding in vitro and in red blood cells.
• Crowding leads to substantial increases in macromolecular activity under confined conditions.
• Small changes in water content can cause large shifts in macromolecular activity in crowded cellular environments.

Conclusions:

• Molecular crowding and confinement are crucial factors influencing cellular processes.
• While established in red blood cells, the role of crowding in complex cell osmotic regulation remains an open research question.
• Further extensive research is warranted to fully elucidate the impact of macromolecular crowding in diverse cellular systems.