Self-organizing molecules in cells: New insights into how cells function

New research is shedding light on the intriguing organization of molecules within living cells. The crowded interior of cells, filled with large and complex molecules, poses a fascinating puzzle for scientists. By studying how these molecules spontaneously organize themselves, we can gain a better understanding of how cells manage their essential biochemistry in such a packed space. This research also has the potential to provide insights into the origins of the first living systems and how they evolved into the intricate structures we see today.

Within eukaryotic cells, which include our own cells, organized structures known as organelles are present. These organelles are enclosed by a lipid membrane and serve various functions. For example, mitochondria, one type of organelle, are responsible for generating energy within cells. Recent discoveries have revealed that groups of molecules can also come together to form temporary organelles, without the need for a membrane, to carry out specific tasks.

Atul Parikh, a professor of biomedical engineering at the University of California, Davis, suggests that there may be simple physical mechanisms at play that allow for the creation of specialized “designer organelles” as needed. Parikh’s laboratory has been investigating this phenomenon using a simplified model of a cell. Their research has demonstrated that mixtures of polymers can undergo phase separation, forming droplets akin to the movement of oils in a lava lamp. These droplets also interact with the cell membrane in unexpected ways, potentially influencing the overall structure of the cell. The findings from this study were published in Nature Chemistry on July 6.

Liquid-liquid phase separation and surface bubbling in vesicles containing a mixture of polyethylene glycol (PEG) and dextran. Credit: Wan-Chih Su, UC Davis

Wan-Chi Su, a graduate student collaborating with Professor Parikh, has made significant progress in the field. Su created artificial vesicles that resemble living cells in size and structure. These vesicles consist of synthetic membranes enclosing water containing two dissolved polymers. Although both polymers dissolve in water, they repel each other, resulting in phase separation if mixed together, much like an unmixed salad dressing.

During their experiments, Su and Parikh observed that as water was withdrawn from the vesicles, the polymers began to form separated droplets as expected. However, instead of growing into larger droplets, they discovered that the interaction between the polymer droplets and the interior of the vesicle membrane hindered their growth. This created a mosaic pattern of droplets within the vesicles.

Interestingly, these interactions also affected the exterior of the vesicles, leading to a bubbling or “blebbing” effect, reminiscent of certain phenomena observed in living cells. Parikh explains that this premature coupling with the vesicle boundary halts phase separation and generates a mosaic of droplets. Furthermore, these three-dimensional droplets inside the vesicles induce rearrangements of molecules within the two-dimensional membrane, thereby signaling to the external environment. The researchers believe that this phenomenon is not limited to specific combinations of molecules but is likely applicable in a broader context.

This study demonstrates how purely physical interactions, such as the repulsion or attraction between polymers, can give rise to intricate organization within a simplified cell-like system. Parikh emphasizes that they are unraveling the underlying physical and chemical principles of biology through their work, which may provide insights into the origins of life itself.

Parikh and his colleagues plan to expand their investigations to more complex systems, including actual living cells. The paper also includes additional authors from UC Davis, Nanyang Technological University in Singapore, and The Pennsylvania State University.

Source: UC Davis

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