What Breaks a Cell’s Ribs Can Make It Stronger
As the mitotic spindle tightens to separate chromosomes during cell division, it produces and absorbs forces.
当有丝分裂纺锤体在细胞分裂过程中收紧以分离染色体时，它会产生并吸收力。
Ada Zejun Shen/ Quanta Magazine
沉泽君/广达杂志
The cells of animals, plants, and fungi start their lives by being torn apart.
动物、植物和真菌的细胞都是通过撕裂开始生命的。
Cells are born by division, and just before a parent cell becomes two daughters, it doubles its nuclear DNA and carefully condenses it into X-shaped chromosomes.
细胞通过分裂而诞生，就在亲代细胞变成两个子代细胞之前，它会将其核DNA加倍，并小心地将其浓缩成X形染色体。
The nucleus disassembles, letting these crucial genetic instructions float free in the cell’s soupy interior.
细胞核分解，让这些重要的遗传指令在细胞的糊状内部自由漂浮。
Then the cell performs an astounding, microscopic feat of strength.
然后，细胞就会发挥出惊人的微观力量。
Proteinaceous cables extend from the cell’s poles toward the equator and latch onto the chromosomes.
蛋白质电缆从细胞的两极向赤道延伸并附着在染色体上。
They drag, tilt, and nudge the precious cargo until every chromosome has been ushered into a tidy line around the cell’s middle.
它们拖动、倾斜和轻推珍贵的货物，直到每条染色体都被引导成围绕细胞中部的整齐的线。
Then this spindle apparatus, as it’s known — a sinewy, dynamic rib cage made of bundles of microtubules — shortens itself at both poles.
然后，众所周知，这个纺锤体装置——一个由微管束组成的强健、动态的胸腔——在两极自行缩短。
This wrenches the chromosomes apart into two sets and reels them to opposite ends of the cytoplasm sea.
这会将染色体分成两组，并将它们卷到细胞质海的两端。
With its genetic material segregated at either pole, one cell can safely become two, born from a microscopic tug-of-war.
由于其遗传物质在任一极分离，一个细胞可以安全地变成两个细胞，通过微观的拉锯战诞生。
The spindle strains against itself as it shortens and pulls; how it does this without ripping itself apart has been a scientific mystery since biophysicists first observed cell division with microscopes 150 years ago.
主轴在缩短和拉动时会对其自身施加压力；自从 150 年前生物物理学家首次用显微镜观察到细胞分裂以来，它如何在不分裂的情况下做到这一点一直是一个科学谜团。
“They saw them [the chromosomes] moving, which led to this idea that there’s probably forces that are pulling or pushing things around,” said Colleen Caldwell , a biophysicist at the University of Groningen.
格罗宁根大学生物物理学家科琳·考德威尔 (Colleen Caldwell) 表示：“他们看到染色体在移动，从而产生了这样的想法：可能存在拉动或推动物体的力。”
If absorbing those forces caused the spindle’s integrity to fail, it could spell the end for both daughter cells or cause diseases that arise from errors in cell division and chromosome arrangement.
如果吸收这些力导致纺锤体的完整性失效，则可能意味着两个子细胞的终结，或导致因细胞分裂和染色体排列错误而引起的疾病。
In this way, all eukaryotic life , including human life, rides on the spindle’s success with each cell division across an organism’s lifetime.
这样，所有真核生命，包括人类生命，都依赖于生物体一生中每次细胞分裂的纺锤体的成功。
Until recently, researchers didn’t have the tools to physically manipulate the mammalian spindle structure at the subcellular scale to toy with it and find out how it works.
直到最近，研究人员还没有在亚细胞尺度上物理操纵哺乳动物纺锤体结构的工具来摆弄它并找出它是如何工作的。
Recently a team of researchers led by Sophie Dumont , a biophysicist at the University of California, San Francisco, used microneedles to physically manipulate and stress the structure in mammal cells for the first time — and then observe how the spindle holds together through intense strain as it wrenches the chromosomes apart.
最近，由加州大学旧金山分校生物物理学家 Sophie Dumont 领导的研究小组首次使用微针对哺乳动物细胞的结构进行物理操纵和施加压力，然后观察纺锤体在将染色体扭断时如何通过强烈的张力保持在一起。
Sophie Dumont is the first researcher to physically probe the workings of the mitotic spindle in a mammalian cell.
索菲·杜蒙 (Sophie Dumont) 是第一位对哺乳动物细胞有丝分裂纺锤体的运作进行物理探索的研究人员。
The experiments have shown how a self-repair mechanism enables the spindle to stabilize itself under force and avoid disintegrating.
实验表明，自我修复机制如何使主轴在外力作用下稳定自身并避免解体。
These findings, which were published in February 2026 in Current Biology , provide a window into the physics of the cellular world, where complex living machines endure physical forces and stresses like machines in a factory.
这些发现于 2026 年 2 月发表在《当代生物学》杂志上，为了解细胞世界的物理学提供了一个窗口，在细胞世界中，复杂的生命机器像工厂里的机器一样承受物理力和压力。
The spindle’s mechanical quirks show just how weird materials science can get at the finest scales of life.
主轴的机械怪癖表明，材料科学可以在生命的最精细尺度上达到多么奇怪的程度。
By virtue of being biological, the cell spindle presents massive complexity for materials physicists.
由于具有生物性，细胞纺锤体对材料物理学家来说呈现出巨大的复杂性。
Most human-made materials contain just a few different types of molecules, said Colm Kelleher , a biophysicist at Syracuse University who was not involved with the new research.
雪城大学的生物物理学家科尔姆·凯莱赫（Colm Kelleher）没有参与这项新研究，他说，大多数人造材料只含有几种不同类型的分子。
Meanwhile, the spindle is made of hundreds of different types of individual protein molecules, and any one of them is “an extremely complex object,” he said.
与此同时，纺锤体由数百种不同类型的单个蛋白质分子组成，其中任何一个都是“一个极其复杂的物体”，他说。
That puts the spindle in an unusual size class that complicates experiments.
这使得主轴处于一个不寻常的尺寸级别，使实验变得复杂。
“There’s quite a bit that scientists know about the mechanics of individual molecules, and there’s quite a bit that scientists know about the mechanics of tissues and organisms, like how muscles generate force,” Dumont said.
“科学家们对单个分子的力学了解很多，而且科学家对组织和生物体的力学了解很多，比如肌肉如何产生力量，”杜蒙特说。
“But mechanics at this scale of many molecules together forming this macromolecular structure is harder to probe.
“但是许多分子共同形成这种大分子结构的这种规模的力学更难探测。
So we know less about it, but it’s just as important.”
所以我们对此知之甚少，但它同样重要。”
One last wrinkle is that, by being part of a living organism, these biomolecular structures are constantly consuming energy from within the materials themselves — very unlike how human-made materials and machines work.
最后一个问题是，作为活有机体的一部分，这些生物分子结构不断消耗材料本身内部的能量——这与人造材料和机器的工作方式非常不同。
Kelleher gave the example of a car: It has a fuel tank and an engine, which power components that transfer torque to the wheels, which then push against the ground.
凯莱赫举了汽车的例子：它有一个油箱和一个发动机，为将扭矩传递到车轮的组件提供动力，然后车轮推动地面。
A system made of biological materials works very differently.
由生物材料制成的系统的工作原理非常不同。
“It would be like if you had a car where there were only wheels, and you injected the gasoline directly into the wheel, and it all started moving itself,” he said.
“这就像如果你有一辆只有轮子的汽车，你将汽油直接注入轮子，然后一切就开始自行移动，”他说。
“The force-generating components, the energy-consuming components, and the force-transferring components are all physically mixed up with each other.”
“产生力的部分、消耗能量的部分和传递力的部分在物理上都是相互混合的。”
Despite the mechanical oddities inherent to living machines, investigations into spindle physics have been going on for decades.
尽管活体机器存在固有的机械怪异，但对主轴物理的研究已经持续了数十年。
In the 1960s, the late Duke University biologist Bruce Niklas started using extremely fine glass needles to probe and manipulate chromosomes in living cells by pushing from the outside against the cell membrane.
20 世纪 60 年代，已故杜克大学生物学家 Bruce Niklas 开始使用极细的玻璃针，通过从外部推动细胞膜来探测和操纵活细胞中的染色体。
By exerting physical force on the spindle and chromosomes, he and his colleagues revealed some of the key mechanics for the first time.
通过对纺锤体和染色体施加物理力，他和他的同事首次揭示了一些关键机制。
For example, tension on the kinetochores — the disc-shaped proteins to which the spindle’s fibers attach on the chromosome — is thought to let the cell confirm the spindle’s correct attachment and ensure the proper separation of chromosomes during cell division.
例如，着丝粒（纺锤体纤维附着在染色体上的圆盘状蛋白质）上的张力被认为可以让细胞确认纺锤体的正确附着，并确保细胞分裂过程中染色体的正确分离。
The stages of cell division.
细胞分裂的阶段。
The cell spindle (green) attaches to the chromosomes at their kinetochores (pink).
细胞纺锤体（绿色）附着在染色体的动粒（粉色）上。
It lines them up in the middle of the cell and then pulls them apart to opposite poles.
它将它们排列在细胞的中间，然后将它们拉向相反的两极。
Then the cell splits into two.
然后细胞分裂成两部分。
Wellcome Images/Science Source
惠康图片/科学来源
Over the next few decades, Niklas’ work prodding and pulling on the fibers started the field of spindle mechanics, Dumont said.
杜蒙特说，在接下来的几十年里，尼克拉斯对纤维进行刺和拉的工作开启了纺锤力学领域。
He is “basically our hero,” she added.
她补充说，他“基本上是我们的英雄”。
His work opened up questions about how the spindle generates force, how much force it can produce, and how it responds to any forces the environment exerts on it.
他的工作提出了有关主轴如何产生力、它能产生多少力以及它如何响应环境施加在其上的任何力的问题。
Normally when you pull on something, it breaks.
通常，当您拉动某物时，它就会破裂。
But here, pulling makes the material stronger.
但在这里，拉力使材料变得更坚固。
However, his work was done in a very specific type of cell: grasshopper spermatocytes, the progenitors of grasshopper sperm cells.
然而，他的工作是在一种非常特殊的细胞类型中完成的：蚱蜢精母细胞，蚱蜢精子细胞的祖细胞。
These cells had some experimental benefits.
这些细胞有一些实验上的好处。
They tolerate physical manipulation with glass microneedles, for instance, and have large, easily observable chromosomes.
例如，它们可以耐受玻璃微针的物理操作，并且拥有易于观察的大染色体。
But Dumont wanted to look beyond insects to find out know how the spindle behaves in mammalian cells like ours.
但杜蒙希望超越昆虫，了解纺锤体在像我们这样的哺乳动物细胞中的行为方式。
She needed to find a type of mammal cell that, like Niklas’ grasshopper spermatocytes, had large but relatively few chromosomes and were amenable to manipulation by microneedles.
她需要找到一种哺乳动物细胞，就像尼克拉斯的蚱蜢精母细胞一样，具有较大但相对较少的染色体，并且易于通过微针操作。
The cells of rat kangaroos, rabbit-size nocturnal marsupials, have only 12 or 13 chromosomes depending on the sex.
大鼠袋鼠（兔子大小的夜行性有袋动物）的细胞只有 12 或 13 条染色体，具体取决于性别。
They turned out to be ideal.
结果证明他们是理想的。
For approximately 10 years, Dumont’s lab has tugged on rat kangaroo cells with microneedles — “sometimes we call it cell torture,” she said — to see how they respond to different forces.
大约十年来，杜蒙的实验室一直用微针拉扯大鼠袋鼠细胞——“有时我们称之为细胞折磨，”她说——以观察它们对不同力量的反应。
In 2020, her team got a surprise.
2020年，她的团队得到了惊喜。
When they yanked on the fiber with the microneedle, it did not detach from the chromosome or from the spindle’s anchor points at the cell’s poles.
当他们用微针拉动纤维时，它没有与染色体或细胞两极的纺锤体锚点分离。
The fiber broke in the middle, like a pencil snapping in two.
纤维从中间断裂，就像铅笔断成两半一样。
What’s more, the ragged ends of the busted fibers didn’t immediately unravel.
更重要的是，断裂纤维的粗糙末端并没有立即散开。
They settled into a stable form, like a nylon rope whose frayed end has been melted to stop further disintegration.
它们形成了稳定的形态，就像一根尼龙绳，其磨损的一端已被熔化以阻止进一步分解。
Caleb Rux , a bioengineer in the Dumont lab, looked more closely at how the fibers were breaking and somehow being stabilized afterward.
杜蒙实验室的生物工程师 Caleb Rux 更仔细地观察了纤维是如何断裂以及随后以某种方式稳定下来的。
To manipulate the spindle with extreme precision, he used what looked like a video game controller to lower a motorized microneedle and move it in any direction in 62.5-nanometer increments.
为了极其精确地操纵主轴，他使用看起来像视频游戏控制器的东西来降低电动微针，并以 62.5 纳米的增量向任意方向移动。
The researchers broke the mitotic spindle (stained pink) by tugging on the structure with a microneedle from the outside of the cell membrane without piercing it.
研究人员通过用微针从细胞膜外部拉动结构而不刺穿有丝分裂纺锤体（染成粉红色）来打破它。
The video has been sped up; its length is 3:40 minutes.
视频已被加速；它的长度是3分40秒。
“I think of it as like a 3D Etch a Sketch,” Rux said.
“我认为它就像 3D 蚀刻草图，”Rux 说。
The faster the needles were programmed to move and pull against the spindle fibers, the more force they applied.
针被编程为移动和拉动纺锤纤维的速度越快，它们施加的力就越大。
Rux, Dumont, and their colleagues found that when fibers were cut with lasers, which don’t exert a tugging force, they became unstable and fell apart.
Rux、Dumont 和他们的同事发现，当用激光切割光纤时，由于激光不施加拉力，它们会变得不稳定并散开。
But fibers that were first stressed and stretched with a microneedle and then cut in that spot with a laser were able to stabilize.
但首先用微针施加压力和拉伸，然后用激光在该点切割的纤维能够稳定下来。
Dumont’s team wondered whether there was a kind of automatic repair mechanism that could heal spans of the fiber when it was subjected to force.
杜蒙的团队想知道是否存在一种自动修复机制，可以在纤维受到力时修复其跨度。
The spindle fibers are microtubules, which are essentially long rods made up of many tiny interlocking components.
纺锤体纤维是微管，本质上是由许多微小的互锁成分组成的长杆。
Rux compared those components to Lego bricks that assemble into a much larger structure.
Rux 将这些组件与组装成更大结构的乐高积木进行了比较。
“Under force, these individual Lego [bricks] might pop out of the structure — not at the end, but literally in the middle of it,” Rux said.
“在外力作用下，这些单独的乐高积木可能会从结构中弹出——不是在末端，而是在结构的中间，”鲁克斯说。
And when they do, more stable bricks in the area could pop in to take their place and stabilize the fiber.
当它们这样做时，该区域更稳定的砖块可能会突然出现，取代它们并稳定纤维。
Caleb Rux led work that revealed the resilience of the mitotic spindle, the critical structure that organizes DNA during cell division.
Caleb Rux 领导的研究揭示了有丝分裂纺锤体的弹性，有丝分裂纺锤体是细胞分裂过程中组织 DNA 的关键结构。
“It took years to get to that mechanism,” he said.
“我们花了好几年的时间才建立起这个机制，”他说。
To test their hypothesis, they needed to know where such repairs might be happening.
为了检验他们的假设，他们需要知道此类修复可能发生在哪里。
They added a fluorescent tag to end-binding protein 1 (EB1), a microtubule-associated protein that prefers to bind to stable compounds rather than less stable ones.
他们在末端结合蛋白 1 (EB1) 上添加了荧光标签，这是一种微管相关蛋白，更喜欢与稳定的化合物而不是不太稳定的化合物结合。
The fiber lit up with this protein at the exact same spot where force was being exerted, suggesting that self-stabilization was occurring.
纤维在施加力的同一位置上被这种蛋白质点亮，表明正在发生自稳定。
“It took years to get to that mechanism,” Rux said.
“我们花了好几年的时间才达到这个机制，”鲁克斯说。
“It was really exciting and made me feel vindicated that all the reading and work we’d done had actually led us down the right road.”
“这真的很令人兴奋，让我觉得我们所做的所有阅读和工作实际上都引导我们走上了正确的道路。”
He hypothesizes that when force is applied to the spindle fiber, the stretching and pulling makes it jettison some of its smaller cytoskeletal components — the Lego bricks — which get pushed out into the surrounding cytoplasm.
他假设，当对纺锤体纤维施加力时，拉伸和拉动会使其抛弃一些较小的细胞骨架成分（乐高积木），这些成分被推入周围的细胞质中。
At the same time, other, more stable bricks suspended in the cytoplasm can pop into the injured structures and reinforce them.
与此同时，悬浮在细胞质中的其他更稳定的砖块可以突然进入受损的结构并加固它们。
This makes the entire spindle structure more stable precisely where it needs support.
这使得整个主轴结构在需要支撑的地方更加稳定。
This may be an automatic process, Rux said, or specific proteins might encourage the microtubule bricks to fill the gaps.
鲁克斯说，这可能是一个自动过程，或者特定的蛋白质可能会促使微管砖填补空白。
The phenomenon is a bit counterintuitive.
这种现象有点违反直觉。
Alexander Mogilner , a computational biologist at New York University who was not involved in the study, compared it to a finger trap.
纽约大学计算生物学家亚历山大·莫吉尔纳（Alexander Mogilner）没有参与这项研究，他将其比作手指陷阱。
Normally when you pull on something, it breaks.
通常，当您拉动某物时，它就会破裂。
But here, pulling makes the material stronger.
但在这里，拉力使材料变得更坚固。
“The brute message of the study is kind of heartwarming — that the external forces would stabilize the spindle and make it more resilient,” he said.
他说：“这项研究传达的粗暴信息有点温暖人心——外力会稳定主轴并使其更具弹性。”
This mechanism may explain how the spindle manages to exert and withstand the forces generated when it plays chromosomal tug-of-war.
这种机制可以解释纺锤体如何在进行染色体拔河比赛时设法施加和承受所产生的力。
The spindle’s life, after all, is a bit of a paradox, Dumont said.
杜蒙特说，毕竟主轴的寿命有点矛盾。
“It has to be a dynamic structure to build itself, to move chromosomes, to remodel, yet it has to be strong,” she said.
“它必须是一个动态结构来构建自身、移动染色体、重塑，但它必须很坚固，”她说。
Perhaps a workable solution is to spontaneously gird and stabilize itself when generating and absorbing force.
也许一个可行的解决方案是在产生和吸收力时自发地束紧并稳定自身。
The lesson of spindle resilience extends beyond the biological.
纺锤体弹性的教训超出了生物学范围。
Rux used to work as a mechanical engineer inspecting roads for cracks that result from use and weathering.
Rux 曾经是一名机械工程师，负责检查道路是否因使用和风化而出现裂缝。
He now wonders if it’d be possible to engineer roads that grow stronger under load, rather than more fragile over time.
他现在想知道是否有可能设计出在负载下变得更坚固的道路，而不是随着时间的推移变得更加脆弱。
“Biology’s had billions of years to evolve these structures to be really robust and good at their jobs,” he said.
他说：“生物学花了数十亿年的时间来进化这些结构，使其变得非常强大并擅长发挥其作用。”
“I think there are things to be learned from some of these principles, and [we can] use [them] to inspire some of our engineered systems as well.”
“我认为从这些原则中可以学到一些东西，并且[我们可以]利用[它们]来启发我们的一些工程系统。”
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