LIFE IN A CROWDED ENVIRONMENT
Although biochemical reactions have been largely studied in the context of purified proteins in dilute solutions, the molecular environment inside living cells is completely different. The cytoplasm is highly crowded environment chock full of components including ribosomes, large protein or protein-RNA complexes, filamentous cytoskeletal elements, as well as membranous and non-membranous organelles of diverse sizes. This crowded nature of the cytoplasm may hinder movement of large complexes while allowing for movement of small proteins or molecules. Crowding may also contribute to the mechanical properties of the cell and organization of components through phase separations. As we are interested in how cellular processes perform in the context of living cells, we see crowding as an important but largely unappreciated parameter that could have a large impact on the biology of living cells.
Inspired by our recent unpublished results showing that cytoplasmic density can vary in cells (Knapp et al., in preparation), we are interested addressing questions such as:
How does cytoplasmic density affect cellular processes such as microtubule dynamics, endocytosis or growth?
Does cytoplasmic density change in cells, for instance at different stages of the cell cycle, or in response to certain perturbations or physiological states? What types of molecules are involved in controlling or contributing to cytoplasmic density?
Is the nucleoplasm crowded in a similar manner as the cytoplasm? How does crowding in the nucleus impact chromosomal dynamics and chromosomal processes.
To address these types of questions, we are developing new quantitative assays for measuring cellular density, crowding, and mechanical properties of cells. We are also developing approaches to experimentally manipulate crowding/density. We hope that our studies in fission yeast and other model organisms will allow us to begin to define general concepts in this newly developing field.