Cells Use ‘Disordered’ Proteins to Control Access to the Nucleus

Scientists watching the nuclear pore in action
discover that its moving protein filaments form
a highly selective traffic control system.

 

The Cell’s Nuclear Gate Runs on Organized Disorder

By John D. Wise, PhD

I recently gave a talk for the Institute for Scientific and Biblical Research (ISBR) in Frederick, Maryland. The talk drew in part from research by Almassalha et al. that I discussed in my earlier Creation Evolution Headlines article (12 Jan 2026) on chromatin geometry.

As an illustration, I showed a short animation from Wikimedia Commons. The camera zooms toward the nucleus of a cell and then plunges through one of the openings in the nuclear envelope.

At that point I paused the video.

“That,” I told the audience, “is not a simple hole, as this video shows it.”

What appears to be an empty opening is in reality one of the most elaborate molecular machines in the cell: the nuclear pore complex (NPC). It is the gate that regulates traffic between the nucleus and the rest of the cell.

Not Just a Hole in the Nuclear Envelope

The very next day I encountered an article in Quanta Magazine, “Disorder Drives One of Nature’s Most Complex Machines,” March 9, 2026, describing fresh research on how this remarkable structure works.

Every nuclear pore complex is constructed from hundreds of proteins, of around 30 different types. From the front, it looks like an eight-petaled flower; from the side, like a flying saucer. Its center opening spills over with spaghetti-like proteins tethered to the inner walls of the complex.

“It’s a thing of enormous beauty,” said Brian Chait, a chemical biologist at Rockefeller University. “It’s marvelous. It’s a wonder. … It’s phenomenal.”

The Quanta article reports recent work published in Nature Cell Biology, “Karyopherins remodel the dynamic organization of the nuclear pore complex transport barrier,” 2 December, 2025, by Toshiya Kozai, et al.

Watching the Nuclear Pore in Motion

Using high-speed atomic force microscopy, the researchers were able to observe the interior of the nuclear pore complex at millisecond time scales. What they saw challenges earlier static pictures of the pore.

The transport channel is neither a rigid tunnel nor a mechanical valve. Instead, it is filled with a dense forest of flexible proteins called FG-nucleoporins[1] (one of which is our old friend Nup98, a remarkably versatile nucleoporin involved not only in nuclear transport but also in gene regulation!). This forest of flexible proteins forms a fluctuating polymer network across the opening. Within this moving mesh lies a denser region often called the Central Plug. Rather than being a fixed structure, this plug reflects the constantly shifting organization of the FG network itself.

Molecular Couriers and the Forest of Filaments

Cargo-carrying transport proteins known as karyopherins move through this network as molecular couriers. These proteins, whose family includes both the importins that carry cargo into the nucleus and the exportins that carry cargo out, are not structural parts of the pore complex. Instead, they are mobile transport receptors that repeatedly pass through it. As the authors report, karyopherins “remodel the dynamic organization of the FG-nucleoporin network,” transiently reorganizing the fluctuating filaments as they move through the channel.

Think of karyopherins as molecular couriers with a specialized key to the forest. The dense thicket of FG filaments blocks most molecules through sheer physical interference. Karyopherins, however, possess a specific chemical affinity for those filaments. By binding briefly to the moving FG chains, they reorganize the surrounding mesh and open a transient pathway through the network. In effect, the couriers do not simply push through the forest; they momentarily reshape it, effectively ‘unzipping’ the disorder just long enough to pass their cargo through.

When “Disorder” Becomes a Design Feature

This is where the 4D Nucleome meets Systems Biology. The nuclear pore is not merely a static three-dimensional structure; it is a four-dimensional filter in which time and motion are part of the architecture itself. In the older reductionist view, “disorder” looked like a flaw. In the systems-view now emerging, this organized fluctuation is a feature. The moving FG network allows the cell to maintain what is effectively a software-defined gate, one capable of adapting its shape to thousands of different molecular “passwords” every second.

The nuclear pore complex is one of the largest molecular assemblies in the cell. Thousands of these structures perforate the nuclear envelope of a typical nucleus. Through each of these gates, hundreds to thousands of molecules may pass every second while the system still maintains strict selectivity.

The Quanta headline emphasizes “disorder,” and in one sense that description is accurate:

… in the center of the nuclear pore complex, “everything is mediated by disorder,” said Patrick Onck, a computational physicist at the University of Groningen in the Netherlands. “It’s not order that generates this function. It’s disorder.”

The FG-nucleoporins that fill the pore’s transport channel behave like flexible polymer chains, constantly moving and fluctuating within the channel. Yet the experiments reveal something more subtle than simple randomness. These filaments collectively form a dynamic mesh whose organization shifts as transport receptors pass through it. What appears at first glance to be molecular chaos is better understood as regulated motion within a highly coordinated system.

A Motivation for Systems Biology

The design inference suggested by discoveries like this in recent decades has pushed biology into uncomfortable territory. One response has been the rise of Systems Biology, which studies living systems as integrated networks rather than as collections of isolated parts.

In recent years, discoveries across cell biology have repeatedly revealed systems that operate through controlled dynamics rather than rigid machinery. Chromatin loops bring distant genes and regulatory elements into contact. Membrane-less cellular compartments assemble through liquid phase separation (LLPS). Many regulatory proteins are intrinsically disordered yet perform highly specific functions.

The nuclear pore complex now joins this growing list of biological systems in which flexibility and motion are not signs of disorder but tools of regulation. Specifically, we now see that the “disorder” is half of a sophisticated dialogue.

The Hole That Wasn’t Empty

To the casual viewer of a cell animation, the nuclear pore looks like an empty opening in the nuclear envelope. But as researchers probe deeper, that apparent hole resolves into one of the most intricate molecular gateways known in biology.[2] Every second, thousands of molecules pass through these portals, guided by a shifting forest of flexible proteins that maintain strict selectivity through a “software-defined” dance.

Far from dissolving biological order, these new observations highlight a recurring lesson of modern cell biology: the closer scientists look, the more the cell reveals layers of coordinated design operating across multiple levels at once.

The history of biology is the history of “simple” things becoming impossibly complex the moment we look closer. We used to think the cell was a blob of simple protoplasm. We used to think non-coding DNA was “junk.” Now, we find that even the “holes” in the nucleus are filled with a shimmering, finely calibrated system.

As it turns out, what looks like chaos to the untrained eye is actually a high-speed linguistic processor – one that reads the molecular “syntax” of every traveler before letting them pass. We aren’t looking at disorder; we are looking at a complex design-language we have only just begun to learn to read.

Footnotes

[1] FG-nucleoporins are one of a class of Intrinsically disordered proteins (IDPs). I have become increasingly fascinated with IDPs over the last few months. They are proteins that lack a fixed three-dimensional structure and instead exist as constantly shifting conformations. First recognized in the 1990s when certain regulatory proteins resisted crystallization and structural analysis, IDPs are now known to play major roles in cellular signaling and regulation. Their flexibility allows them to form transient interactions with multiple partners. They are also major components of liquid phase separations (LLPS), which is receiving a great deal of scientific attention at the moment. FG-nucleoporins are flexible IDP filaments that line the nuclear pore and interact dynamically with transport proteins.

Intrinsically disordered proteins are relatively rare in bacteria but abundant in eukaryotes, where their flexible structures allow cells to build large, dynamic regulatory networks involving transient interactions and rapid signaling responses.

[2] I strongly suggest readers go to the Quanta article. It has two remarkable illustrations of the structure and working of the NPC.

---

John Wise received his PhD in philosophy from the University of CA, Irvine in 2004. His dissertation was titled Sartre’s Phenomenological Ontology and the German Idealist Tradition. His area of specialization is 19th to early 20th century continental philosophy.

He tells the story of his 25-year odyssey from atheism to Christianity in the book, Through the Looking Glass: The Imploding of an Atheist Professor’s Worldview (available on Amazon). Since his return to Christ, his research interests include developing a Christian (YEC) philosophy of science and the integration of all human knowledge with God’s word.

He has taught philosophy for the University of CA, Irvine, East Stroudsburg University of PA, Grand Canyon University, American Intercontinental University, and Ashford University. He currently teaches online for the University of Arizona, Global Campus, and is a member of the Heterodox Academy. He and his wife Jenny are known online as The Christian Atheist with a podcast of that name, in addition to a YouTube channel: John and Jenny Wise.