Bourbon Street and Macromolecular Crowding

On Saturday evening a parade—the Krewe du Vieux—bore its way through the French Quarter, featuring a menagerie of individuals dressed in a wide array of colorful outfits. In particular, the Krewe du Vieux is known for its satirical element, taking on politics with a rather heavy dose of absurdity. Of course, as is to be expected for any sort of Mardi Gras event, the streets were lined with eager observers. But crowds are no stranger to the French Quarter: anyone who has walked down Bourbon Street at night can attest to the dense thicket that inevitably grounds movement to a halt in some places. To the layperson, these crowds represent something crossed between a delight and a nuisance. To a biophysicist, these crowds provide a particularly interesting case study—what can we learn about biophysics from observing the crowds of Bourbon Street?

With crowds comes disorder and ultimately, in New Orleans particularly, debauchery. It’s no secret that excessive macromolecular crowding has potentially deleterious effects on proteins, resulting in their misfolding and loss of native function. Here, at least in part, I’m talking about amyloidogenic diseases such as Alzheimer’s and Parkinson’s. Proteins (or peptides) such as Aβ, which are typically benign in isolation, can aggregate under high concentration conditions and form toxic plaques. This applies as well to many other proteins, which will aggregate and misfold beyond a certain critical macromolecular concentration.

The viscosity of the cellular milieu is noted in the Biophysical Journal Best of 2016 volume, which attendees of the Biophysical Society Annual Meeting 2017 received as part of their welcome materials bag. In the first article of this volume, Jennifer L. Ross wrote about the so-called “dark matter” of biology—components within the cell that are difficult to measure yet have potentially profound effects. Along this vein, we must remember that biomolecules do not exist in isolation. To some degree, crowding effects within the cell are tolerated and can even help a protein collapse into its native state. As Dr. Ross surmises, in some fashion cells may even be able to exert control over local crowding. Chaperones, for instance, allow some degree of control as misfolded proteins are able to be reconfigured back into their native conformations.

The topic of crowding is covered several times over the course of this year’s meeting. For instance, on Tuesday at 12:10 PM in room 206/207, Jeanne Stachowiak will be discussing the impact of membrane-protein crowding on spontaneous membrane fission events, and a poster by Niraja Kedia on Monday will present research into the effect of crowding agents on Aβ oligomer structure. If your interest is piqued, consult this year’s program, and you’ll be happy to find that there are many other platforms and posters relevant to this topic.

As a final word, I recommend that you embrace the opportunity to extract comparisons between the vibrant city around us and biophysics. Whether gazing upon the Mississippi River and dreaming of fluid dynamics (a bit on the nose?), channeling yourself from one side of the city to another across the transport machinery that is the New Orleans streetcar, or dreaming of a crowded cellular environment while amidst the throes of people stumbling down Bourbon Street, there exist parallels between macro- and microscopic life. Go out, explore, (be safe), and have fun.

Chris Lockhart

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