Disorder Drives One of Nature’s Most Complex Machines
The inner channel of the nuclear pore complex in all its messy glory.
核孔复合体的内部通道尽显凌乱的光彩。
Far from a simple pore, the complex is filled with dynamic proteins that move molecules into and out of the nucleus.
该复合物远非简单的孔，而是充满了动态蛋白质，可将分子移入和移出细胞核。
In this computer model, green strands represent disordered nucleoporin proteins and blue knots are karyopherin transport proteins.
在该计算机模型中，绿色链代表无序核孔蛋白，蓝色结代表核转运蛋白。
At the dawn of complex life, evolution created a container for DNA, its most treasured item.
在复杂生命诞生之初，进化创造了 DNA 的容器，这是它最珍贵的物品。
A few billion years later, 20th-century microscopists looked at this container — the nucleus — up close and saw that it was covered in tiny openings.
几十亿年后，20 世纪的显微镜学家近距离观察了这个容器——原子核，发现它被微小的开口覆盖。
At the time, they didn’t know what to make of these structures, but as microscopy improved, something grand came into focus: what we now call “nuclear pore complexes,” some of the largest and most marvelous molecular machines ever formed.
当时，他们不知道如何构建这些结构，但随着显微镜的改进，一些宏伟的东西开始成为焦点：我们现在所说的“核孔复合体”，这是有史以来形成的一些最大、最奇妙的分子机器。
Every nuclear pore complex is constructed from hundreds of proteins, of around 30 different types.
每个核孔复合体均由数百种蛋白质构成，大约有 30 种不同类型。
From the front, it looks like an eight-petaled flower; from the side, like a flying saucer.
从正面看，它像一朵八瓣花；从正面看，它像一朵八瓣花。从侧面看，就像一个飞碟。
Its center opening spills over with spaghetti-like proteins tethered to the inner walls of the complex.
它的中心开口溢出了与复合体内壁相连的意大利面条状蛋白质。
“It’s a thing of enormous beauty,” said Brian Chait , a chemical biologist at Rockefeller University.
“这是一件非常美丽的事情，”洛克菲勒大学化学生物学家布莱恩·柴特 (Brian Chait) 说。
“It’s marvelous.
“太棒了。
It’s a wonder.
这是一个奇迹。
…
……
It’s phenomenal.”
这是惊人的。”
This machine has a vital job: directing molecular traffic into and out of the nucleus.
这台机器有一项重要的工作：引导分子交通进出细胞核。
More than an open door, the protein complex recognizes different molecules as they approach — and lets only some through.
这种蛋白质复合物不仅仅是一扇敞开的门，它还能识别不同的分子，并只让其中一些分子通过。
“The nuclear pore complex is ultimately the gatekeeper for the nucleus,” said Roderick Lim , a biophysicist at the University of Basel in Switzerland.
“核孔复合体最终是细胞核的看门人，”瑞士巴塞尔大学的生物物理学家罗德里克·林(Roderick Lim)说。
“Everything that has to get in and out of the nucleus has to go through these pores.”
“所有进出细胞核的东西都必须通过这些毛孔。”
Each pore into the nucleus is guarded by a jumble of proteins.
进入细胞核的每个孔都由一堆蛋白质守护着。
These molecular bouncers work together to determine which VIPs are allowed into the most exclusive organelle of the cell.
这些分子弹跳者共同作用，确定允许哪些 VIP 进入细胞最独特的细胞器。
Nearly every eukaryotic cell has a nucleus punctured with nuclear pore complexes, and the main components of the complex are incredibly conserved across species, from single-celled yeasts to multicellular humans.
几乎每个真核细胞都有一个被核孔复合物刺穿的细胞核，并且该复合物的主要成分在从单细胞酵母到多细胞人类的各个物种中都极其保守。
Evolution “came up with that thing one time and got stuck with it,” said André Hoelz , a structural cell biologist at the California Institute of Technology.
加州理工学院的结构细胞生物学家安德烈·霍尔兹 (André Hoelz) 表示，进化论“曾经想到过这一点，但却陷入了困境”。
A single mammalian nucleus can contain thousands of them.
一个哺乳动物的细胞核可以包含数千个。
Every second, each nuclear pore lets hundreds to thousands of molecules of all shapes and sizes pass through so that they can travel to their destinations to make proteins, regulate genes, and generally help the cell function.
每秒钟，每个核孔都会让成百上千个各种形状和大小的分子通过，以便它们能够前往目的地制造蛋白质、调节基因并总体上帮助细胞发挥功能。
Some large molecules are carried through the channel by proteins, while small ones diffuse across on their own.
一些大分子由蛋白质携带通过通道，而小分子则自行扩散。
And while some effortlessly glide through, to others it is an impenetrable barrier.
虽然有些人可以毫不费力地滑过，但对另一些人来说，这是一个无法逾越的障碍。
How this gate works with such selectivity is a mystery.
这个门如何以如此选择性的方式工作仍然是个谜。
Over decades, biologists have worked out what most of the static parts of the machine look like.
几十年来，生物学家已经弄清楚了机器的大多数静态部件的样子。
But its center is restless, endlessly moving and morphing, which makes it difficult for even the best methods to visualize.
但它的中心是不安宁的，无休止的移动和变形，这使得即使是最好的方法也难以可视化。
That’s gradually changing.
这种情况正在逐渐改变。
In a study published in Nature Cell Biology at the end of 2025, high-resolution microscopy showed the central barrier in motion at millisecond resolution, revealing a flexible structure that constantly rearranges itself.
在 2025 年底《自然细胞生物学》上发表的一项研究中，高分辨率显微镜以毫秒分辨率显示了运动的中心屏障，揭示了不断重新排列的灵活结构。
The experimental imaging, backed by computational modeling , suggests that the function of the nuclear pore complex is guided by flexibility and movement.
由计算模型支持的实验成像表明，核孔复合体的功能是由灵活性和运动引导的。
A nuclear pore complex’s outer ring, which fits into the membrane of a cell’s nucleus, is built from hundreds of proteins of around 30 different types.
核孔复合体的外环适合细胞核的膜，由大约 30 种不同类型的数百种蛋白质构成。
But most of the action flows through its center channel, which allows molecules to enter and exit the nucleus.
但大部分作用都是通过其中心通道进行的，该通道允许分子进出细胞核。
This is more than an intellectual curiosity.
这不仅仅是一种求知欲。
A surge of recent research has linked neurodevelopmental disorders, viral disease, and cancers to problems with the complex.
最近的大量研究将神经发育障碍、病毒性疾病和癌症与该复合体的问题联系起来。
If biologists can discern how its cellular trafficking system works, they could develop methods to stop unwanted pathogens from getting through — and also try to guide therapeutic molecules into the cell nucleus, where the genome itself awaits.
如果生物学家能够辨别其细胞运输系统的工作原理，他们就可以开发出阻止不需要的病原体通过的方法，并尝试引导治疗分子进入细胞核，基因组本身就在细胞核中等待。
“We are starting to approach a near-atomic picture of nuclear pores from various organisms,” said Mike Rout , a cell biologist at Rockefeller University who led the new work that offers insight into a molecular machine at the heart of eukaryotic life.
洛克菲勒大学细胞生物学家迈克·鲁特 (Mike Rout) 表示：“我们正在开始研究各种生物体核孔的近原子图像。”他领导了这项新研究，深入了解了真核生命核心的分子机器。
For many scientists who study the nuclear pore, it was an instant fascination: They were awed that this (relatively) massive biological machine could allow so many kinds of molecules, and so many of them, to move in and out of the nucleus efficiently, with little room for error.
对于许多研究核孔的科学家来说，这立刻让人着迷：他们惊叹于这个（相对）巨大的生物机器可以允许如此多种类的分子，如此多的分子，有效地进出细胞核，几乎没有出错的空间。
“It is beautiful,” Hoelz said.
“它很漂亮，”霍尔茨说。
“How do you generate an aircraft hangar that has a door where a 747 can go through,” but a small marble can’t fly out?
“如何生成一个飞机机库，它有一扇 747 可以通过的门”，但小弹珠却飞不出去？
Somehow the gate itself must play bouncer for life’s important molecules.
不知何故，门本身必须充当生命重要分子的保镖。
RNA molecules must get out of the nucleus to the cytoplasm to make proteins.
RNA分子必须离开细胞核进入细胞质才能制造蛋白质。
Ribosomes, the structures that do the protein-making, are themselves made of molecules assembled in the nucleus and moved out through the pores.
核糖体是制造蛋白质的结构，本身是由在细胞核中组装并通过孔移出的分子组成的。
Meanwhile, molecules involved in regulating the genome must be ushered into the nucleus preferentially.
同时，参与调控基因组的分子必须优先被引入细胞核。
As these processes unfold, the nuclear pore is also blocking things that don’t belong, such as harmful enzymes or misfolded RNAs.
随着这些过程的展开，核孔也会阻挡不属于的东西，例如有害的酶或错误折叠的 RNA。
The cell biologist Mike Rout has spent decades studying the nuclear pore complex.
细胞生物学家迈克·鲁特花了数十年的时间研究核孔复合体。
This vital structure, built from hundreds of individual proteins, is the gatekeeper and traffic controller of a cell’s nucleus.
这种重要的结构由数百个单独的蛋白质组成，是细胞核的看门人和交通控制器。
Lori Chertoff/Rockefeller University
洛里·切尔托夫/洛克菲勒大学
In the decades since the discovery of the nuclear pore complex, biologists have slowly gained a greater understanding of its structure using electron microscopy, tools of physics, and computer modeling.
自从发现核孔复合体以来的几十年里，生物学家利用电子显微镜、物理工具和计算机建模慢慢地对其结构有了更深入的了解。
With the advent of cryo-electron microscopy, a powerful technique that images cells after flash-freezing them, they have been able to assess the static parts of the machine .
随着冷冻电子显微镜的出现，这种强大的技术可以在快速冷冻细胞后对其进行成像，他们已经能够评估机器的静态部分。
These efforts have generated a near-atomic view of each individual protein that builds the eight petal-like radial units.
这些努力已经生成了构建八个花瓣状径向单元的每个单独蛋白质的近原子视图。
But the technique hasn’t worked for the very center, called the transport channel, where most of the pore’s action happens.
但这项技术不适用于被称为传输通道的中心，毛孔的大部分活动都发生在此处。
“Whenever anyone uses some of these microscopes to peer inside nuclear pores, they just see this amorphous cloud inside,” Lim said.
“每当有人使用这些显微镜观察核孔内部时，他们都会看到里面有这种无定形的云，”林说。
“It’s like a haze.”
“就像一片阴霾。”
The reason, which became apparent in the 1990s, is that the center of this giant machine is filled with proteins that have no obvious or specific structure.
原因在 20 世纪 90 年代变得显而易见，因为这台巨型机器的中心充满了没有明显或特定结构的蛋白质。
These proteins, called FG-nucleoporins, have tails that wiggle around like seaweed and that can’t be captured in static images.
这些蛋白质被称为 FG-核孔蛋白，其尾巴像海藻一样摆动，无法在静态图像中捕捉到。
These tails are “the dark matter of the nuclear pore complex,” Hoelz said.
霍尔茨说，这些尾巴是“核孔复合体的暗物质”。
It’s not order that generates this function.
生成此函数的不是顺序。
It’s disorder.
这是混乱。
Patrick Onck, University of Groningen
帕特里克·翁克，格罗宁根大学
Most proteins fold into specific structures or shapes essential to the functions they perform in a cell.
大多数蛋白质折叠成特定的结构或形状，这对于它们在细胞中执行的功能至关重要。
But intrinsically disordered proteins , a category that includes these nucleoporins, don’t have a single structure.
但本质上无序的蛋白质（包括这些核孔蛋白的一类）并不具有单一结构。
They flail about, changing shape and binding to different molecules.
它们四处游动，改变形状并与不同的分子结合。
This means that 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.
荷兰格罗宁根大学计算物理学家帕特里克·昂克说，这意味着在核孔复合体的中心，“一切都是由无序介导的”。
“It’s not order that generates this function.
“产生这个函数的不是顺序。
It’s disorder.”
这是混乱。”
In the early 2000s, the field was awash with bickering about the organization and behavior of FG-nucleoporins in the transport channel and how they might traffic molecules into and out of the nucleus.
2000 年代初，该领域充满了关于 FG 核孔蛋白在运输通道中的组织和行为以及它们如何将分子运入和运出细胞核的争论。
Researchers agreed that most macromolecules can’t get through the channel without the help of cargo-carrying proteins called transport factors.
研究人员一致认为，如果没有被称为运输因子的载货蛋白质的帮助，大多数大分子就无法通过该通道。
Transport factors, which mingle with the nucleoporins in the channel, bind only to those molecules that include a specific short stretch of amino acids — a molecular tag that “says, in effect, ‘send me into the nucleus,’” Rout said.
转运因子与通道中的核孔蛋白混合，仅与那些包含特定短氨基酸片段的分子结合——这是一种分子标签，“实际上说，‘把我送进细胞核’，”劳特说。
But researchers differed on how the channel itself might be organized, which would impact how molecules move through it.
但研究人员对于通道本身的组织方式存在分歧，这将影响分子通过通道的方式。
Some argued that nucleoporins snap onto one another, forming a gel-like mesh network.
一些人认为核孔蛋白彼此卡合，形成凝胶状的网状网络。
Others argued that the disordered proteins don’t interact with each other much, but rather constantly undulate like bristles on a brush.
其他人则认为，无序的蛋白质彼此之间相互作用不多，而是像刷子上的刷毛一样不断波动。
The debate became contentious.
辩论变得有争议。
“It used to be very hostile,” Hoelz recalled.
“它曾经非常充满敌意，”霍尔茨回忆道。
“People are very passionate about what they’re doing.
“人们对他们正在做的事情非常热情。
It’s not a personal animosity.”
这不是个人恩怨。”
“For a very long time, it was like, ‘Are you a gel person, or are you a brush person?’ You’re one or the other,” said Siegfried Musser , a cell biologist at Texas A&M University.
“很长一段时间以来，人们都在问，‘你是喜欢凝胶的人，还是喜欢刷子的人？’你是其中之一，”德克萨斯农工大学的细胞生物学家西格弗里德·穆塞尔 (Siegfried Musser) 说。
The biophysicist Roderick Lim and his team used high-speed atomic force microscopy to image the inner workings of the nuclear pore complex.
生物物理学家 Roderick Lim 和他的团队使用高速原子力显微镜对核孔复合体的内部运作进行成像。
Biozentrum, University of Basel
巴塞尔大学生物中心
In recent years, new collaborations and discussions, including at an annual conference where the principals gather to chat, have quieted the conflict.
近年来，新的合作和讨论，包括在校长们聚集在一起聊天的年度会议上，已经平息了冲突。
But the truth about the structure and functioning of the transport channel hadn’t been resolved.
但有关传输通道的结构和功能的真相尚未得到解决。
The researchers would need to get more creative to understand how the complex functions in its native environment.
研究人员需要发挥更大的创造力来了解复杂的系统在其原生环境中如何发挥作用。
“We wanted to simply go back to the nuclear pore complex and really ask the nuclear pore to tell us what it’s doing,” Rout said, “not for us to impose on it what it’s doing.”
“我们只想回到核孔复合体，真正要求核孔告诉我们它在做什么，”劳特说，“而不是让我们强加给它它在做什么。”
How do you interrogate a molecular complex?
如何探究分子复合物？
Rout and Lim, who have both advocated for a more dynamic model of the nuclear pore, started with a simple idea: Poke it.
Rout 和 Lim 都主张建立更动态的核孔模型，他们从一个简单的想法开始：戳它。
Rout has spent decades characterizing yeast pore complexes.
劳特花了几十年的时间来表征酵母孔复合物。
Lim is an expert on high-speed atomic force microscopy, a technique that runs a very sharp probe over a surface, lightly and rapidly tapping it, to get a sense of how it moves.
Lim 是高速原子力显微镜方面的专家，这种技术可以在表面上运行非常锋利的探针，轻轻快速地敲击它，以了解它是如何移动的。
A few years ago, in a dark basement laboratory, Lim’s graduate student Toshiya Kozai began unpacking plastic vials containing millions of yeast nuclear pore complexes.
几年前，在一个黑暗的地下室实验室中，林的研究生 Toshiya Kozai 开始打开装有数百万个酵母核孔复合物的塑料瓶。
He toiled for days in the “dungeon of our department,” Lim recalled, working nonstop to get the samples into the high-speed atomic force microscope while they were fresh.
林回忆道，他在“我们部门的地牢”里辛苦工作了好几天，马不停蹄地工作，以便在样本新鲜时将它们送入高速原子力显微镜。
“It’s a real labor of love.”
“这是真正的爱的劳动。”
His efforts enabled the team to watch the transport channel change, millisecond by millisecond.
他的努力使团队能够逐毫秒地观察传输通道的变化。
“We could see very clear, super rapid motion,” Rout recalled.
“我们可以看到非常清晰、超快速的运动，”劳特回忆道。
The resulting videos may look blurry to us macroscopic creatures, but they are some of the highest-definition looks at the behavior of the nanoscopic transport channel.
由此产生的视频对于我们宏观生物来说可能看起来很模糊，但它们是纳米级传输通道行为的最高分辨率的观察。
Lim used high-speed atomic force microscopy, which taps a probe over a molecule’s surface, to create this real-time video of the transport channel of a yeast nuclear pore complex.
Lim 使用高速原子力显微镜，用探针敲击分子表面，创建了酵母核孔复合体传输通道的实时视频。
The pink arrow points to the central plug — an elusive structure in the pore that, until now, hadn’t been confirmed.
粉红色箭头指向中央塞子——孔中的一个难以捉摸的结构，直到现在还没有得到证实。
Nature Cell Biology 27, 2089-2101 (2025)
自然细胞生物学 27, 2089-2101 (2025)
At the edges of the channel, near the walls, Rout and Lim’s team saw rapid fluctuations of molecules — those were the wiggly nucleoporins.
在通道边缘靠近墙壁的地方，Rout 和 Lim 的团队看到了分子的快速波动——这些分子就是摆动的核孔蛋白。
At the center they saw a fuzzy blob, known as the central plug, that continuously moved around and repositioned itself within the transport channel.
在中心，他们看到了一个模糊的斑点，称为中央塞，它在传输通道内不断移动并重新定位。
For a long time, biologists had suspected that a central plug might exist, but in previous microscopy images it wasn’t always visible.
很长一段时间以来，生物学家一直怀疑可能存在一个中心塞，但在之前的显微镜图像中它并不总是可见。
“Seeing is believing,” said Hoelz, who was not involved in the study.
“眼见为实，”霍尔茨说，他没有参与这项研究。
To be able to show this “is a beautiful thing.”
能够展示这一点“是一件美丽的事情”。
Led by Chait and using mass spectrometry, the team discovered that the plug was made of transport proteins called karyopherins, or “kaps” for short, plus their molecular cargo.
在 Chait 的带领下，研究小组利用质谱分析发现，该栓塞是由称为核转运蛋白（karyopherins）（简称“kaps”）的运输蛋白及其分子货物组成的。
As kaps move through the nuclear pore, they latch onto the nucleoporins, tugging them toward the channel’s center.
当 Kaps 穿过核孔时，它们会抓住核孔蛋白，将它们拉向通道的中心。
This creates a temporary, dynamic obstacle that slows other molecules or stops them from moving through.
这会产生一个临时的动态障碍，减慢其他分子的速度或阻止它们移动。
In that way, kaps not only help carry molecules across, but also push away anything that’s not supposed to be there, Rout said.
劳特说，通过这种方式，kaps 不仅可以帮助携带分子，还可以推开任何不应该存在的东西。
When they added in more transport factors, they saw the plug grow bigger.
当他们添加更多的运输因素时，他们发现塞子变得更大。
The heart of the nuclear pore complex is being constantly rearranged by kaps, creating an ever-changing environment.
核孔复合体的核心不断被 kaps 重新排列，创造出一个不断变化的环境。
The results suggest that the pore’s organization and behavior are much more dynamic than a gel network, Rout said, and much closer to a brushlike environment.
劳特说，结果表明，孔隙的组织和行为比凝胶网络更具动态性，并且更接近刷状环境。
The findings support a model he previously proposed called the “virtual gate” in which the dynamics of the environment is critical for directing proteins away or through.
这些发现支持了他之前提出的称为“虚拟门”的模型，其中环境的动态对于引导蛋白质离开或通过至关重要。
He likened it to a crowded dance floor.
他将其比作拥挤的舞池。
The inner channel of the nuclear pore complex is organized by disordered nucleoporin proteins (green), which lack a stable structure.
核孔复合体的内部通道由无序的核孔蛋白（绿色）组织，缺乏稳定的结构。
Cargo-carrying transport proteins (pink) interact with the dynamic nucleoporins to shuffle molecular cargo (not pictured) through the pore to go into and out of the nucleus.
携带货物的转运蛋白（粉红色）与动态核孔蛋白相互作用，将分子货物（未图示）通过孔进出细胞核。
Animation by Enrique Sahagun, Scixel
动画由 Enrique Sahagun、Scixel 制作
“If you know how to dance, you can simply enter the dance and swing from partner to partner, holding hands, just quickly exchanging going across,” he said.
“如果你知道如何跳舞，你可以简单地进入舞蹈并从一个舞伴摇摆到另一个舞伴，手牵着手，快速交换跨越，”他说。
“If you don’t know how to dance, all you see is this turbulent melee, and you try to get in.
“如果你不知道如何跳舞，你看到的只是这场动荡的混战，你会试图融入其中。
No one’s taking hold of you to help you enter the dance, so you just get pushed away.”
没有人抓住你来帮助你进入舞蹈，所以你只是被推开了。”
To further test their observations, Rout and Lim created synthetic pores the same size as natural nuclear pore complexes.
为了进一步测试他们的观察结果，Rout 和 Lim 创建了与天然核孔复合体大小相同的合成孔。
When they tethered nucleoporins inside and added transport factors, the synthetic pores behaved like the wild yeast nuclear pore complexes.
当它们将核孔蛋白束缚在内部并添加运输因子时，合成孔的行为就像野生酵母核孔复合体一样。
They saw the central plug appear.
他们看到中央插头出现了。
“What I find actually very striking is that they reproduce the result with a very simple model,” Musser said.
“我发现实际上非常惊人的是他们用一个非常简单的模型重现了结果，”马瑟说。
“It’s a pretty stunning result.”
“这是一个相当惊人的结果。”
Hoelz is not totally convinced that this is a nail in the coffin for the gel model.
霍尔兹并不完全相信这对凝胶模型来说是致命的。
The “answer is [probably] somewhere in the middle, which is very often the case in science,” he said.
“答案可能是介于两者之间，这在科学中很常见，”他说。
Researchers likely catch the central channel in different configurations because it’s changing all the time, he suggested, or perhaps the inner channels of some nuclear pores are more like a gel and others are more like a brush.
他认为，研究人员可能会捕捉到不同结构的中央通道，因为它一直在变化，或者某些核孔的内部通道可能更像凝胶，而另一些则更像刷子。
One recent modeling study led by Onck and published in Nature Communications suggested that the central transport channel could have some parts that are brushlike and others that are similar to condensates — membraneless, liquidlike compartments that have characteristics of gels and brushes.
最近由 Onck 领导并发表在《自然通讯》上的一项模型研究表明，中央传输通道可能有一些像刷子一样的部分，而其他部分则类似于冷凝物——无膜、液体状的隔室，具有凝胶和刷子的特征。
It could even be the case that the channel’s denser center has qualities more like a gel or condensate, Musser said, while the periphery is more brush-like.
马瑟说，甚至可能出现这样的情况：通道较致密的中心具有更像凝胶或凝结物的性质，而外围则更像刷子。
Hoelz said that only new technologies that can fully see inside the pore will resolve the debate — and they could come any day now.
霍尔兹表示，只有能够完全看到毛孔内部的新技术才能解决这一争论——而且它们随时可能出现。
“People are constantly trying to develop new tools or new strategies to try to figure out what’s going on,” Musser agreed.
“人们不断尝试开发新工具或新策略，试图弄清楚正在发生什么，”马瑟表示同意。
In 2025, he and his team published results in Nature that used a powerful 3D imaging tool called Minflux to trace molecules in high resolution as they move through nuclear pore complexes in intact nuclei of human cells.
2025 年，他和他的团队在《自然》杂志上发表了研究结果，使用名为 Minflux 的强大 3D 成像工具以高分辨率追踪分子穿过人类细胞完整细胞核中的核孔复合物。
Learning of this method was “a complete game changer for me,” said Hoelz, who was not involved.
没有参与其中的霍尔茨说，学习这种方法“对我来说彻底改变了游戏规则”。
Musser’s team observed molecules moving only near the edge of the transport channel.
马瑟的团队观察到分子仅在传输通道边缘附近移动。
This also complements Rout and Lim’s study, given that the central plug might be blocking the center.
这也补充了 Rout 和 Lim 的研究，因为中央插头可能会阻塞中心。
“But it doesn’t make sense for the middle not to be used,” Musser said.
“但不使用中间部分是没有意义的，”穆瑟说。
“I think we just haven’t found the right substrate or developed the right tools to see stuff go through the middle.”
“我认为我们只是还没有找到合适的基材或开发出合适的工具来让东西穿过中间。”
No matter what the inside looks like, it’s clear that the nuclear pore complex is incredibly malleable and robust — which also makes it the cell’s “Achilles’ heel,” Rout said.
劳特说，无论内部是什么样子，核孔复合体显然具有令人难以置信的可塑性和坚固性，这也使其成为细胞的“阿喀琉斯之踵”。
It is critical to a cell’s health, and central to its most important processes: protein production and gene regulation.
它对于细胞的健康至关重要，并且是细胞最重要过程的核心：蛋白质生产和基因调控。
But because it is resilient and can endure damage, it can be altered by disease without shutting down.
但由于它具有弹性并且可以承受损坏，因此它可以在疾病发生时改变而不需要关闭。
Some proteins that make up the nuclear pore “show up again and again and again as weak spots for disease,” Rout said, including neurodevelopmental disorders, viral diseases, and cancers.
劳特说，构成核孔的一些蛋白质“一次又一次地作为疾病的弱点出现”，包括神经发育障碍、病毒性疾病和癌症。
Both cancer cells and viruses likely interfere with proteins in the complex to swing the protein-making machinery in their favor or shut down an immune response.
癌细胞和病毒都可能干扰复合物中的蛋白质，从而使蛋白质制造机制向有利于它们的方向转变或关闭免疫反应。
In that sense, the nuclear pore complex is far more than a molecular gate.
从这个意义上说，核孔复合体不仅仅是一个分子门。
“It’s a nexus for integration of information,” Rout said.
“这是信息整合的纽带，”劳特说。
“And I think if the cell had thoughts, that would be how it thinks of its nuclear pores.”
“而且我认为，如果细胞有思想，它就会如何思考它的核孔。”
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