(Macro)Molecular Crowding

This book presents a comprehensive overview of macromolecular crowding, a fundamental biological phenomenon that arises from the high concentration of macromolecules, such as proteins, nucleic acids, and carbohydrates, within living cells. Such crowded environment significantly reduces the amount of free water and alters key physical properties of media, such as viscosity and water activity. One of the most notable effects is volume exclusion, where the space taken up by macromolecules becomes unavailable to others, influencing molecular interactions and reaction dynamics.

Cellular crowding can dramatically impact the stability and behavior of biological macromolecules, affect their folding, aggregation, and association, as well as alter the rates of chemical reactions. However, these effects are still not fully understood, largely because traditional biochemical research is conducted in dilute solutions failing to replicate the crowded conditions inside cells.

To address this gap, researchers are developing experimental models that simulate macromolecular crowding and confinement, allowing for more accurate studies of biomolecular behavior under realistic conditions. These models are essential for understanding how crowding influences molecular function and cellular processes.

Recent discoveries have revealed that macromolecular crowding is not uniform throughout the cell. Instead, it exhibits spatio-temporal heterogeneity, with regions of extreme crowding formed by membrane-less organelles and biological condensates—dense liquid droplets created through liquid-liquid phase separation. These dynamic structures often emerge in response to environmental changes and play critical roles in cellular organization and regulation.

This book brings together leading experts to explore the foundational principles and cutting-edge developments in this field. It covers the physics of crowding, experimental techniques for characterizing these phenomena, and examples of well-understood systems. It also serves as a practical guide for researchers, helping them design experiments and generate hypotheses relevant to their study systems.

Designed for both early-career scientists and those entering the field from other disciplines, this volume offers a structured and accessible introduction to macromolecular crowding. It provides curated access to essential literature and equips readers with the tools needed to navigate this complex and rapidly evolving area of research.