内容来源：https://www.quantamagazine.org/what-breaks-a-cells-ribs-can-make-it-stronger-20260629/

内容总结：

细胞“肋骨”断裂，反而更强？科学家揭示细胞分裂中的自我修复机制

动物、植物和真菌的细胞，其生命始于一场撕裂——细胞通过分裂诞生。在母细胞一分为二之前，它会复制核DNA并将其压缩成X形染色体，随后核膜解体，使这些至关重要的遗传指令漂浮在细胞质中。紧接着，细胞上演一场微观层面的力量壮举：由微管束构成的纺锤体结构（被称为细胞的“肋骨”），从细胞两极伸出蛋白质缆索，抓住染色体并拖拽、倾斜，最终将所有染色体整齐排列在细胞中央。随后，纺锤体在两端同时缩短，像拔河一样将染色体分成两组，拉向细胞质的两极，最终一个细胞安全地分裂为两个。

150年来，生物物理学家一直困惑于纺锤体在缩短和拉扯过程中如何承受巨大的张力而不自我撕裂。荷兰格罗宁根大学的生物物理学家科琳·考德威尔指出，早期科学家观察到染色体移动，便推测存在某种力量在推拉它们。如果纺锤体因承受力而完整性受损，可能导致两个子细胞死亡，或引发因细胞分裂和染色体排列错误导致的疾病。可以说，包括人类在内的所有真核生物的生命，都依赖于每次细胞分裂时纺锤体的成功运作。

由于缺乏在亚细胞尺度上物理操纵哺乳动物纺锤体结构的工具，相关研究长期停滞。近日，加州大学旧金山分校的生物物理学家索菲·杜蒙领导的团队，首次利用微针在哺乳动物细胞中物理操纵并施压纺锤体结构，观察其在强力拉扯染色体时如何保持完整。实验表明，一种自我修复机制使纺锤体在受力时能够稳定自身，避免解体。这一成果于2026年2月发表在《当代生物学》上，为理解细胞世界的物理学提供了窗口——在这个世界中，复杂的生命机器如同工厂里的机械，承受着物理力的作用。

活体材料的力学之谜

从材料物理学的角度看，细胞纺锤体极为复杂。雪城大学的生物物理学家科尔姆·凯莱赫指出，大多数人造材料仅含少数几种分子，而纺锤体由数百种不同的蛋白质分子构成，每一种都堪称“极其复杂的物体”。这种特殊尺度增加了实验难度。杜蒙表示，科学家对单个分子的力学以及组织和器官（如肌肉如何产生力）的力学已有不少了解，但介于两者之间、由众多分子共同组成大分子结构的力学，更难探测，因此所知甚少，却同样重要。

更特殊的是，作为生命体的一部分，纺锤体这类生物分子结构会不断消耗材料内部的能量，与人造材料和机器截然不同。凯莱赫用汽车作比喻：汽车有油箱和引擎，驱动部件将扭矩传递到车轮，车轮再推动地面。而生物材料系统则完全不同：“就像一辆只有车轮的汽车，你把汽油直接注入车轮，它就开始自己动起来——产生力的部件、消耗能量的部件和传递力的部件全都混在一起。”

尽管存在这些力学特性，对纺锤体物理的研究已持续数十年。20世纪60年代，已故杜克大学生物学家布鲁斯·尼克斯就曾用极细的玻璃针从细胞膜外推压，来探测和操纵活细胞中的染色体。他和同事首次揭示了关键力学机制，例如纺锤体纤维与染色体连接的圆盘状蛋白（着丝粒）上的张力，被认为能让细胞确认纺锤体正确附着，确保染色体正常分离。杜蒙称尼克斯为“我们的英雄”，他的工作开启了关于纺锤体如何产生力、能产生多大力量以及如何响应环境力的研究。不过，尼克斯的实验对象是蚱蜢精母细胞，杜蒙则希望探究哺乳动物细胞中纺锤体的行为。最终，她选择了染色体数量较少（仅12或13条）的鼠袋鼠细胞，经过约10年的“细胞酷刑”实验，观察其受力反应。

断裂后更强：纺锤体的“自愈”机制

2020年，杜蒙团队意外发现：当用微针拉扯纺锤体纤维时，纤维并未从染色体或细胞极的锚点脱落，而是在中间断裂，像铅笔断成两截。更关键的是，断裂的纤维毛边并未立即散开，而是稳定下来，如同尼龙绳被熔化的末端阻止进一步解体。该实验室的生物工程师凯莱布·拉克斯进一步观察了纤维断裂及随后稳定的过程。他使用类似游戏手柄的装置，以62.5纳米为精度操控电动微针。拉克斯发现，用激光切割（不施加拉力）的纤维会变得不稳定并解体；而先用微针拉伸施力、再在相同位置用激光切割的纤维却能稳定下来。

团队推测，可能存在一种自动修复机制，能在纤维受力时“治愈”损伤。纺锤体纤维（微管）由许多相互锁定的小组件（类似乐高积木）组成。拉克斯解释，在力的作用下，某些“积木”可能从结构中间弹出，而周围更稳定的“积木”会填补空缺，使纤维稳定。为验证这一假设，他们用荧光标记追踪一种微管相关蛋白（EB1），该蛋白偏好与稳定化合物结合。结果显示，纤维在受力点发出荧光，表明自我稳定过程确实发生。拉克斯认为，施力会使纤维抛出一些小组件到细胞质中，同时细胞质中更稳定的组件会“嵌入”受损结构，进行加固——这可能是自动过程，也可能有特定蛋白质引导。

纽约大学的计算生物学家亚历山大·莫吉内尔将这一现象比作“手指陷阱”：通常拉扯会导致断裂，但在这里拉扯却让材料更强。杜蒙表示，纺锤体必须既是动态结构以完成自我构建和染色体移动，又必须足够坚固。这种自我修复机制可能解释了纺锤体如何在“染色体拔河”中产生并承受巨大张力。

纺锤体的“韧性启示”已超出生物学范畴。曾从事道路裂缝检测的拉克斯现在思考：能否设计出在负载下反而更强、而非随时间脆弱化的道路？“生物学花了数十亿年进化出如此稳健高效的结构，”他说，“我们可以从这些原理中学习，并用于启发工程系统。”

中文翻译：

细胞的“肋骨”受损后反而更强韧
引言
动物、植物和真菌的细胞通过撕裂自身开始生命。细胞通过分裂诞生，而在一个母细胞分裂为两个子细胞之前，它会复制核内DNA，并小心地将DNA凝聚成X形的染色体。细胞核解体，使这些至关重要的遗传指令在细胞黏稠的内部环境中自由漂浮。随后，细胞会完成一项惊人的微观力量壮举。
由蛋白质构成的缆索从细胞两极向赤道延伸，并抓住染色体。它们拖拽、倾斜并推动这些珍贵物质，直到每条染色体都被引导至细胞中央整齐排列。接着，这种被称为纺锤体的结构——一个由微管束构成的强韧而动态的“胸腔”——在两端缩短。这会将染色体撕扯成两组，并分别拉向细胞质海的两端。当遗传物质在细胞两极分离后，一个细胞便能安全地分裂为两个，而这源于一场微观的“拔河比赛”。
纺锤体在缩短和拉扯时承受着巨大的张力；自150年前生物物理学家首次通过显微镜观察细胞分裂以来，它如何避免撕裂自身一直是一个科学谜题。“他们看到染色体在移动，这让人联想到可能有力在拉或推着它们移动，”格罗宁根大学的生物物理学家科琳·考德威尔说。
如果承受这些力导致纺锤体的完整性受损，可能意味着两个子细胞的终结，或引发因细胞分裂和染色体排列错误导致的疾病。因此，所有真核生物——包括人类——的生命都依赖纺锤体在生物体一生中每次细胞分裂时的成功运作。
直到最近，研究人员仍缺乏在亚细胞尺度上物理操控哺乳动物纺锤体结构、摆弄它并探究其工作原理的工具。近日，由加州大学旧金山分校生物物理学家索菲·杜蒙领导的研究团队首次使用微针物理操控并施压于哺乳动物细胞中的纺锤体结构，并观察它如何在高强度拉扯中保持完整。
这些实验揭示了一种自我修复机制，使纺锤体在受力时能稳定自身并避免解体。这些发现于2026年2月发表在《当代生物学》上，为了解细胞世界的物理学提供了窗口——其中复杂的生命机器像工厂中的机器一样承受物理力和应力。纺锤体的力学特性表明，在生命最细微的尺度上，材料科学可以变得多么奇特。

一种活体材料
作为生物结构，细胞纺锤体给材料物理学家带来了巨大的复杂性。雪城大学的生物物理学家科尔姆·凯莱赫（未参与这项新研究）表示，大多数人造材料只包含几种不同类型的分子，而纺锤体则由数百种不同的单个蛋白质分子构成，其中任何一种都是“极其复杂的物体”。
这使得纺锤体处于一个不同寻常的尺寸类别，增加了实验的复杂性。“科学家对单个分子的力学了解颇多，对组织和器官（如肌肉如何产生力）的力学也了解颇多，”杜蒙说，“但在多个分子共同构成这种大分子结构的尺度上，力学更难探测。因此我们了解较少，但它同样重要。”
另一个复杂之处在于，作为生命体的一部分，这些生物分子结构会不断消耗材料内部自身的能量——这与人类制造的材料和机器的工作方式截然不同。凯莱赫以汽车为例：它有油箱和发动机，驱动部件将扭矩传递到车轮，车轮再推动地面。而由生物材料构成的系统则完全不同。
“这就像一辆只有车轮的汽车，你直接把汽油注入车轮，然后它自己开始移动，”他说，“产生力的部件、消耗能量的部件和传递力的部件都物理性地混合在一起。”
尽管生命机器固有这些力学特性，对纺锤体物理学的研究已进行了数十年。20世纪60年代，已故杜克大学生物学家布鲁斯·尼克拉开始使用极细的玻璃针，从外部推动细胞膜来探测和操控活细胞中的染色体。通过对纺锤体和染色体施加物理力，他与同事首次揭示了一些关键力学原理。例如，着丝粒（纺锤体纤维附着在染色体上的盘状蛋白质）上的张力被认为能让细胞确认纺锤体的正确附着，并确保细胞分裂时染色体的正确分离。
杜蒙表示，在接下来的几十年里，尼克拉对纤维进行戳拉的研究开启了纺锤体力学领域。他“基本上是我们的英雄”，她补充道。他的工作引发了关于纺锤体如何产生力、能产生多大的力、以及如何对环境施加的力作出反应的问题。
然而，他的研究是在一种特定类型的细胞中进行的：蚱蜢精母细胞，即蚱蜢精子的前体细胞。这些细胞在实验中有一些优势。例如，它们能承受玻璃微针的物理操控，并且拥有较大且易于观察的染色体。但杜蒙希望跳出昆虫范畴，了解纺锤体在哺乳动物细胞（如我们人类细胞）中的行为。她需要找到一种哺乳动物细胞，像尼克拉的蚱蜢精母细胞一样，具有较大但数量较少的染色体，并且适合用微针操控。
袋鼠鼠（一种兔大小的夜行有袋动物）的细胞根据性别只有12或13条染色体。它们被证明是理想的研究对象。大约10年来，杜蒙的实验室用微针拖拽袋鼠鼠细胞——“有时我们称之为细胞酷刑，”她说——以观察它们对不同力的反应。

纺锤体的韧性
2020年，她的团队意外发现。当他们用微针猛拉纤维时，它并没有从染色体或纺锤体在细胞两极的锚点上脱落。纤维从中间断裂，像铅笔被掰成两段。更重要的是，断裂纤维参差不齐的末端并未立即散开。它们稳定下来，就像一根尼龙绳的磨损末端被熔化以防止进一步解体。
杜蒙实验室的生物工程师凯莱布·拉克斯更仔细地观察了纤维如何断裂并随后以某种方式稳定下来。为了以极高精度操控纺锤体，他使用了一个类似视频游戏手柄的装置，将电动微针降低并以62.5纳米的增量向任意方向移动。
“我认为它就像一台3D蚀刻素描机，”拉克斯说。微针被编程移动和拉扯纺锤体纤维的速度越快，它们施加的力就越大。
拉克斯、杜蒙及其同事发现，当纤维被激光切割（不施加剧烈的拉扯力）时，它们变得不稳定并解体。但那些首先被微针施加应力并拉伸、而后在相同位置用激光切割的纤维却能保持稳定。
杜蒙的团队想知道是否存在一种自动修复机制，能在纤维受力时修复其跨度。纺锤体纤维是微管，本质上是由许多微小互锁组件组成的长杆。拉克斯将这些组件比作乐高积木，它们组装成更大的结构。“在力的作用下，这些单个乐高积木可能从结构中弹出——不是在末端，而是正好在中间，”拉克斯说。当它们弹出时，该区域更稳定的积木可以替换它们的位置并稳定纤维。
为了验证这一假设，他们需要知道修复可能发生的位置。他们向末端结合蛋白1（EB1）添加了荧光标记，EB1是一种微管相关蛋白，倾向于结合稳定化合物而非不稳定化合物。纤维在受力点恰好发出这种蛋白的荧光，表明自我稳定正在发生。
“花了数年时间才弄清这个机制，”拉克斯说。“这非常激动人心，让我觉得我们所有的阅读和工作确实引领我们走上了正确的道路。”
他假设，当纺锤体纤维受力时，拉伸和拉扯会使其丢弃一些较小的细胞骨架组件——即乐高积木——这些组件被推出到周围的细胞质中。同时，悬浮在细胞质中的其他更稳定的积木可以嵌入受损结构并加固它们。这使得整个纺锤体结构在需要支撑的地方正好变得更加稳定。拉克斯说，这可能是一个自动过程，或者特定蛋白质可能促使微管积木填补空隙。
这一现象有点反直觉。未参与该研究的纽约大学计算生物学家亚历山大·莫吉尔纳将其比作“手指陷阱”（一种玩具，越拉越紧）。通常，当你拉扯某物时，它会断裂。但在这里，拉扯使材料更强。“这项研究的核心信息令人感到温暖——即外力会稳定纺锤体，使其更具韧性，”他说。
这种机制可能解释了纺锤体如何在染色体拔河时产生并承受力。毕竟，纺锤体的生存有点矛盾，杜蒙说。
“它必须是一个动态结构，以构建自身、移动染色体、重塑自身，同时它又必须坚固，”她说。或许一个可行的解决方案是在产生和吸收力时自发地加固和稳定自身。
纺锤体韧性的启示超越了生物学范畴。拉克斯曾是一名机械工程师，负责检查因使用和风化而出现裂缝的道路。他现在想知道是否可能建造出在负载下变得更坚固而不是随时间变得更脆弱的道路。
“生物学有数十亿年的时间进化出这些结构，使它们非常稳健且高效地完成工作，”他说。“我认为可以从这些原理中学到一些东西，并利用它们来启发我们的一些工程系统。”

英文来源：

What Breaks a Cell’s Ribs Can Make It Stronger
Introduction
The cells of animals, plants, and fungi start their lives by being torn apart. 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. The nucleus disassembles, letting these crucial genetic instructions float free in the cell’s soupy interior. Then the cell performs an astounding, microscopic feat of strength.
Proteinaceous cables extend from the cell’s poles toward the equator and latch onto the chromosomes. They drag, tilt, and nudge the precious cargo until every chromosome has been ushered into a tidy line around the cell’s middle. Then this spindle apparatus, as it’s known — a sinewy, dynamic rib cage made of bundles of microtubules — shortens itself at both poles. This wrenches the chromosomes apart into two sets and reels them to opposite ends of the cytoplasm sea. With its genetic material segregated at either pole, one cell can safely become two, born from a microscopic tug-of-war.
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. “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.
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. In this way, all eukaryotic life, including human life, rides on the spindle’s success with each cell division across an organism’s lifetime.
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. 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.
The experiments have shown how a self-repair mechanism enables the spindle to stabilize itself under force and avoid disintegrating. 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. The spindle’s mechanical quirks show just how weird materials science can get at the finest scales of life.
A Living Material
By virtue of being biological, the cell spindle presents massive complexity for materials physicists. 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. 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.
That puts the spindle in an unusual size class that complicates experiments. “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. “But mechanics at this scale of many molecules together forming this macromolecular structure is harder to probe. So we know less about it, but it’s just as important.”
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. 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. A system made of biological materials works very differently.
“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. “The force-generating components, the energy-consuming components, and the force-transferring components are all physically mixed up with each other.”
Despite the mechanical oddities inherent to living machines, investigations into spindle physics have been going on for decades. 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. By exerting physical force on the spindle and chromosomes, he and his colleagues revealed some of the key mechanics for the first time. 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.
Over the next few decades, Niklas’ work prodding and pulling on the fibers started the field of spindle mechanics, Dumont said. He is “basically our hero,” she added. 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.
However, his work was done in a very specific type of cell: grasshopper spermatocytes, the progenitors of grasshopper sperm cells. These cells had some experimental benefits. They tolerate physical manipulation with glass microneedles, for instance, and have large, easily observable chromosomes. But Dumont wanted to look beyond insects to find out know how the spindle behaves in mammalian cells like ours. 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.
The cells of rat kangaroos, rabbit-size nocturnal marsupials, have only 12 or 13 chromosomes depending on the sex. They turned out to be ideal. 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.
A Spindle’s Resilience
In 2020, her team got a surprise. 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. The fiber broke in the middle, like a pencil snapping in two. What’s more, the ragged ends of the busted fibers didn’t immediately unravel. They settled into a stable form, like a nylon rope whose frayed end has been melted to stop further disintegration.
Caleb Rux, a bioengineer in the Dumont lab, looked more closely at how the fibers were breaking and somehow being stabilized afterward. 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.
“I think of it as like a 3D Etch a Sketch,” Rux said. The faster the needles were programmed to move and pull against the spindle fibers, the more force they applied.
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. But fibers that were first stressed and stretched with a microneedle and then cut in that spot with a laser were able to stabilize.
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. The spindle fibers are microtubules, which are essentially long rods made up of many tiny interlocking components. Rux compared those components to Lego bricks that assemble into a much larger structure. “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. And when they do, more stable bricks in the area could pop in to take their place and stabilize the fiber.
Elisabeth Fall
To test their hypothesis, they needed to know where such repairs might be happening. 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. The fiber lit up with this protein at the exact same spot where force was being exerted, suggesting that self-stabilization was occurring.
“It took years to get to that mechanism,” Rux said. “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.”
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. At the same time, other, more stable bricks suspended in the cytoplasm can pop into the injured structures and reinforce them. This makes the entire spindle structure more stable precisely where it needs support. This may be an automatic process, Rux said, or specific proteins might encourage the microtubule bricks to fill the gaps.
The phenomenon is a bit counterintuitive. Alexander Mogilner, a computational biologist at New York University who was not involved in the study, compared it to a finger trap. Normally when you pull on something, it breaks. But here, pulling makes the material stronger. “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.
This mechanism may explain how the spindle manages to exert and withstand the forces generated when it plays chromosomal tug-of-war. The spindle’s life, after all, is a bit of a paradox, Dumont said.
“It has to be a dynamic structure to build itself, to move chromosomes, to remodel, yet it has to be strong,” she said. Perhaps a workable solution is to spontaneously gird and stabilize itself when generating and absorbing force.
The lesson of spindle resilience extends beyond the biological. Rux used to work as a mechanical engineer inspecting roads for cracks that result from use and weathering. He now wonders if it’d be possible to engineer roads that grow stronger under load, rather than more fragile over time.
“Biology’s had billions of years to evolve these structures to be really robust and good at their jobs,” he said. “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.”