Chapter 1: Introduction to Biomolecular Condensates

Cellular condensates present a unique aspect of cellular organization, representing a distinct dimension of functionality within cells.

Biomolecular Condensate Formation by Veronica Verdile, Elisa De Paola, and Maria Paola Paronetto

Most of us recall a classic depiction of the cell from our school days: a large blob containing a nucleus, nucleolus, endoplasmic reticulum, Golgi apparatus, vacuoles, mitochondria, and perhaps a lysosome or some cytoskeletal elements. However, this representation is a significant oversimplification.

Cells are far more intricate and varied than these illustrations imply. While I recognize that delving into the complexities of protein assemblies and the finer details of cellular function might be overwhelming for young learners, I often wished to have been introduced to these concepts earlier. To bridge that gap, here's a concise overview of biomolecular condensates.

Condensates are tiny (<0.5–1 µm) clusters of proteins, DNA, or RNA that exhibit emergent functions as a collective unit, notably lacking membranes, contrary to traditional illustrations. But how do these structures form? The predominant mechanism is liquid-liquid phase separation, which can occur through mechanical induction or spontaneous processes, leading to the aggregation of molecules into liquid crystals, colloidal emulsions, or gels—similar to how DNA forms condensates during prophase in mitosis. In the context of protein condensates, an increase in local concentration can significantly influence the Michaelis-Menten and occupancy curves, enhancing activity at identical substrate levels.

These condensates can re-dissolve into the cytoplasm once their function is no longer needed, allowing the cell to maintain both spatial and temporal regulation. But what functions do they perform? Quite a lot.

The nucleolus, previously mentioned as the pioneer of condensates, serves as the primary site for ribosome subunit assembly, which is essential for protein synthesis in any cell. However, there is much more to explore. While animal condensates have historically received more attention, plant condensates, though less studied, offer a promising avenue for future research.

Many condensates in plants are involved in RNA regulation, functioning as multi-molecular transcription factors, managing protein levels, and even facilitating their degradation. Notably, most unique plant condensates operate at the seed level.

Within seeds, various highly conserved condensates exist, and their absence can lead to seed failure. For instance, FLOE1 condensates inhibit seed germination under excessively dry conditions, while ARF7/19 condensates mediate the auxin response, thus influencing plant growth. Additionally, P bodies play a crucial role in regulating mRNA decay to prevent an overabundance of proteins, with around 30 known condensates involved.

As plants respond to their changing environments, the adaptability of condensates, which surpasses that of membrane-bound organelles, becomes essential. Besides FLOE1 condensates, these structures also manage responses to heat, salinity, osmosis, hypoxia, and even immune challenges. For example, hyperosmotic stress triggers the condensation of SEU condensates, which subsequently curtail plant growth under adverse conditions—an adaptive pathway not observed in other organisms.

This aspect is particularly exciting from a fundamental research standpoint. In our increasingly unpredictable climate, plants' ability to swiftly react to significant environmental shifts is crucial for agriculture, highlighting the potential for condensate engineering. The SEU condensate could help develop crops resilient to high salinity during droughts, while FLOE1 condensates are vital for controlling seed dormancy, impacting pre-harvest sprouting in cereals. Other condensates may also extend the availability of seasonal vegetables by altering flowering times.

As research progresses, biomolecular condensates in plants represent a promising area with practical applications, contributing to our understanding of emergent cellular functions on a macroscopic scale and offering tools to address one of the critical crises of our time.

P.S. Congratulations to Cell Press on its 50th anniversary! Thank you for your continued contributions to science.

Chapter 2: The Future of Biomolecular Condensates

In this video titled "Rational Design of Multicomponent Biomolecular Condensates," experts discuss innovative strategies for designing these structures.

This video, "How do single molecules move in and out of condensates?" explores the dynamics of molecular movement within these condensate systems.