Cliff Brangwynne (Princeton & HHMI) 1: Liquid Phase Separation in Living Cells

www.ibiology.org/biophysics/l...
Liquid-liquid phase separation drives the formation of membrane-less organelles such as P granules and the nucleolus. Brangwynne explains how this process works and its important role in normal cell function and disease.
How do the tiny, crowded, constantly moving molecules inside of cells come together to form functional structures such as organelles? Dr. Cliff Brangwynne explains that many of the organelles we are familiar with, such as the nucleus and the Golgi apparatus, are membrane bound. However, some organelles, such as P granules and nuclear bodies, are not surrounded by a membrane. Brangwynne and his colleagues have shown that these membrane-less organelles form by liquid-liquid phase separation, in a manner similar to the separation of oil and water. Brangwynne explains that intrinsically disordered regions (IDRs) in proteins can drive phase separation and are likely important for the formation of structures like P granules. Interestingly, IDRs are also found in proteins associated with diseases such as ALS and Alzheimer’s where protein aggregation is thought to be important.
In his second talk, Brangwynne focuses on the formation of the nucleolus; one of several membrane-less bodies found in the nucleus. Brangwynne’s lab was able to show that assembly of the nucleolus also can be described by the physics of phase separation. As they delved deeper into trying to understand this process, they found that a previously unknown nuclear actin network constrained the movement of the droplets that coalesce to form the nucleolus. They also found that surface tension plays a key role in organizing proteins within the nucleolus and may influence the structure of other membrane-less organelles within the cell.
In his final talk, Brangwynne tells us about recent work in which his lab has used light to control phase separation behavior in cells. By linking IDRs from proteins that are known to phase separate to protein domains that weakly oligomerize in response to light, his lab has generated tools that are allowing them to investigate the role of phase separation in different cell processes in many cell types.
Speaker Biography:
Dr. Cliff Brangwynne received his BS in Material Science and Engineering from Carnegie Mellon University and his PhD in Applied Physics from Harvard University. As a post-doctoral fellow at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Brangwynne combined his interests in soft-matter physics and cell biology to investigate the behavior of sub-cellular organelles in C. elegans embryos. This led to Brangwynne’s discovery that intracellular phase separation is an important mechanism underlying the self-assembly of biological materials.
Brangwynne is now an Associate Professor in Chemical and Biological Engineering at Princeton University and an Investigator of the Howard Hughes Medical Institute. His lab continues to investigate how the physical properties of intracellular materials influence their role in biological processes. Brangwynne was awarded the NIH Director’s New Innovator Award in 2012 and a MacArthur Fellowship in 2018 for his ground-breaking research.
Learn more about Brangwynne’s research here:
www.princeton.edu/cbe/people/f...

[@mazin627]

This was great. I came across a term called liquid liquid phase separation in a paper, didn't understand but thanks to this video I now have some insight. Thank you.

[@katenicholls5301]

Thank you SO much for your clarity and for the generosity of your time. I am fascinated.

[@mehdisharifitabar7745]

Hi Cliff, fantastic talk! . thank you

[@ansonoconnor2035]

This video was fantastic. Great explanations and great lecturing.

[@shrishtiwari7750]

Excellent Lecture. Thanks for clearing the basic concept.

[@rickfearn3663]

Cross pollination between physics and biochemistry is so very exciting!!! Thanks for opening our eyes to these exciting developments. Question is what will the future bring? Thanks Dr. Brangwynne.

[@samingzadeh4494]

Loved it. Thank u Prof. Brangwynne!

[@paul3116]

Fantastic talk! Just a small detail I'd like to add: I wouldn't define the Golgi apparatus as 'a funny name', it comes from Camillo Golgi, an italian scientist who discovered this organelle.

[@jamesdriscoll9405]

You have to admit, it's a little funny that he's known for his little apparatus. Seriously, mad props to the pioneers of cellular biology! And whatever it takes to memorize all of this crazy crazy stuff!

[@ankitbioinfo]

Very nice talk. Finally I landed here after hearing the talk of Tony hyman, Frank Julicher and Eric Dufresne.

[@soudaminisahoo8935]

This is indeed helpful to understand LLPS (liquid-liquid phase separation) from a physics point of view.

[@user-qu5jy3ki2b]

membraneless organelle will change many the molecule biology concepts, thanks Cliff Brangwynne

[@benjaminjoshua6235]

Very great lecture. Looking forward to more videos.

[@RanjitDe]

Very helpful for a beginner like me. Thanks.

[@davidgurarie6712]

These are novel and important idea. Thanks for nice intro.

[@moofaca]

Thanks for the great talk!

[@xXRandomPianoXx]

28:38 You said that with a low interaction parameter (high temperature) the system remains in a high entropy/mixed state. And as you raise the interaction parameter, the system will favor phase separation. But the sign on the y-axis is indicating the opposite. In other words, based on the graph, it appears that a low interaction parameter drives the system into phase separation, and so on... Could it be that the interaction parameter is relative? (ie. low interaction between heterogenous molecules (phase separation) vs. low interaction between homogenous molecules (mixed state))?

[@davidkincade7161]

Great stuff!!

[@captainquinine]

this talk was super good

[@anonviewerciv]

Macromolecules as liquids. (15:30) 7:17 21:51 Organelles without (phospholipid) borders.

[@thefalcon217]

What effect does milli meter microwave raditation have on liquid phase seperation, given it can increase hydroxy radicals in water?

[@sukuraluoriver9813]

thanks

[@weiwang7446]

wish I could give 1000 thumb up

[@jamesdriscoll9405]

Everbody gangsta until the phase change

[@Echodonut]

Coo

[@hollya.g.86]

You're a soft squishy robot, not me

[@jatigre1]

I wonder when biology is finally going to admit and understand that without a "spirit" / "IS-BE" there is no life animating-organizing force behind life-forms

[@davidkincade7161]

See “intended evolution”- there is a “life force” as the substrate to physics and chemistry.

[@patldennis]

Huh?