内容来源：https://www.quantamagazine.org/what-physical-life-force-turns-biologys-wheels-20260420/

内容总结：

生命原动力之谜终获破解：细菌“分子马达”如何驱动生命？

在生命演化的长河中，最早的微生物面临着一个根本困境：在微观世界里，水如沥青般粘稠，没有食物时，它们如何移动？数十亿年后，自然选择给出了一个堪称完美的答案——鞭毛马达。这个比赛车飞轮转速更快的分子机器，驱动着细菌的“尾巴”，使其能以每秒自身长度十倍以上的速度游动，或通过随机翻滚改变方向。自上世纪70年代被发现以来，其精妙构造不仅令科学家惊叹，甚至被智能设计论者奉为“不可简化复杂性”的典范。

经过半个世纪的探索，科学家终于在近年揭开了它的核心奥秘。2020年以来，多项突破性研究，特别是借助冷冻电镜技术，首次解析了鞭毛马达各关键部件的分子结构。至2026年3月，最后一块拼图终于就位。

哈佛大学生物物理学家阿拉温坦·塞缪尔指出，这个系统的运行“近乎最优”。鞭毛马达的核心是一个被称为“C环”的蛋白质圆环，其旋转带动鞭毛。而驱动C环的，则是嵌在细胞膜上的“定子”蛋白复合体。每个定子包含一个五边形环，它如同一个旋转闸门。

真正的驱动力，是一种被称为“质子动力”的物理生命力量。细胞通过消耗能量不断将质子泵出，造成细胞内外质子浓度与电荷的差异，形成质子持续向内流动的趋势。这股质子流如同水流推动水车，依次通过定子的五边形闸门，每次推动其旋转十分之一圈，从而带动更大的C环反向旋转，驱动细菌前进。

那么马达如何换向？研究发现，当细菌感知环境恶化时，会修饰一种名为CheY的信号蛋白。该蛋白结合到C环上后，会引发连锁结构变化，使整个C环像发卡一样瞬间切换形态。此时，定子转而推动C环内缘，使其顺时针旋转，导致鞭毛束散开，细菌开始翻滚。待信号解除，C环恢复原状，细菌便继续在新的方向上觅食。

“这是一种将单向动力转化为大物体双向旋转的极其优雅的方式，”现就职于圣犹大儿童研究医院的苏珊·李评价道。

得克萨斯农工大学荣誉教授迈克·曼森感慨，他长达50年的研究终于圆满，“我终于明白这个我研究了半辈子的东西是如何工作的了。”

质子动力概念由生物化学家彼得·米切尔于1961年提出，并因此获得1978年诺贝尔化学奖。它不仅是鞭毛马达的动力源，更是驱动细胞内诸多关键过程的“通用电流”。细胞通过快速泵出质子维持其内低外高的质子梯度，各种分子机器则像河上的水车，利用这股持续流入的质子流做功。

“如果你理解这一点，”曼森总结道，“你基本上就理解了生物学一切活动的基础。”这项研究不仅揭示了一个微观马达的精密机制，更指向了驱动所有生命运转的、统一而优美的物理原力。

中文翻译：

驱动生物运转的物理“生命力”是什么？

引言

你是已知最早的生命形式。周围此刻没有食物。要是能去别处就好了。但你被困住了。真的动弹不得。以你的体型（几微米）来看，水感觉就像焦油，或者说，就像人类最终被困在焦油里的那种感觉。你该怎么办？

[十亿或数十亿年后。] 你找到了完美的解决方案。

字面意义上的完美。

"你可以认为这个系统正在以最优方式运行，"哈佛大学生物物理学家阿拉温丹·塞缪尔说。

进化创造了鞭毛马达，这是一种螺旋桨与大脑的结合体，使单细胞细菌能够向食物源移动。这是一个电动马达，每秒旋转数百转——比赛车发动机中的飞轮还快——以转动一条尾巴状的鞭毛，推动细胞前进。当鞭毛马达逆时针旋转时，它推动细胞在水中每秒移动超过其自身长度十倍或更远的距离。马达也可以顺时针旋转，导致细胞随机翻滚。这个令人惊叹的、能够自我组装、处理信号、切换方向的分子机器如此强大却又如此精简，以至于数十亿年后的今天，地球上几乎每个肠道和水坑中的细菌仍在使用它。

自20世纪70年代细菌鞭毛马达被发现以来，生物学家和神创论者都对其设计惊叹不已，就像中世纪建筑师敬畏地凝视着罗马祖先建造的万神殿穹顶。很难想象十亿年的细菌进化能达到怎样的工程水平，尤其是在细胞代际之间仅间隔20分钟的情况下，这允许了真正天文数字般的突变和试运行。神创论者将细菌鞭毛马达作为智能设计的首要例证——特别是"不可简化的复杂性"概念，他们说，这个生物系统如此复杂，以至于不可能通过达尔文进化论的渐进、逐步过程分阶段产生。

在过去的几十年里，科学家们一直在努力解开鞭毛马达的工作原理——即它如何旋转和切换方向。

现在他们终于成功了。自2020年以来，一系列研究破解了鞭毛马达各部分的分子结构，其中最重要的是那些转动鞭毛基部较大齿轮的小齿轮。这个动态谜题的最后几块拼图直到2026年3月才最终到位。

"我毕生的追求现在实现了，"德克萨斯农工大学生物物理学荣休教授迈克·曼森说，他从20世纪70年代就开始研究鞭毛马达。"我终于理解了这个我研究了50年的东西到底是如何工作的。这大概是最令人满足的事了。"

鞭毛马达的工作原理确实巧妙。但当我开始采访这些科学家，了解他们的发现时，我没想到马达的解释会为我这样寻求机制性、物理解释的人阐明整个生物学。我了解到，这个机器利用了一种我以前不知道（尽管生物物理学家知道）的驱动力——驱动细胞内各种过程的物理"生命力"。这种"质子动力"不仅转动鞭毛马达的齿轮；它是我们所有生命运转的能量来源。

鞭毛马达是由已故的霍华德·伯格发现的，他是一位富有创造力的实验者，职业生涯大部分时间在哈佛度过。伯格在20世纪70年代初开始运用他的物理学训练来理解细菌如何运动。问题是，在显微镜下，大肠杆菌、沙门氏菌和其他运动细菌几乎瞬间就会游出视野。因此，伯格发明并制造了一台自动追踪显微镜，可以在细菌移动时将其保持在视野中。"它记录的是为了将细菌保持在原位而必须对显微镜载物台进行的所有校正，这当然就给出了游泳细菌路径的读数，"曼森说，他于1975年作为博士后加入了伯格的项目。

数据显示，细菌会"奔跑和翻滚"——也就是说，它们在直线游泳和混乱翻滚之间来回切换。伯格提出理论认为，细菌根据游泳时感知到的化学梯度来改变其游泳状态。它们的默认行为是直线游泳。如果糖和其他营养物质的浓度在增加，细胞就继续前进。如果浓度下降，它就翻滚；在新的方向上重新定向后，细菌恢复直线游泳。这个过程使细菌保持在可获取分子的附近，细菌通过其细胞壁和细胞膜上的通道吸收这些分子。

伯格猜测鞭毛马达是一个转子，像螺丝一样转动鞭毛。"他是通过将两个细胞的鞭毛粘在一起，看到它们彼此反向旋转来证明的，"曼森说。"仅凭此，在没有任何相关知识的情况下，他假设细菌鞭毛会旋转。远远超前于他的时代。那是在理解这个马达如何工作的50年前。"

进一步的实验表明，鞭毛马达也会切换方向。当细菌的所有鞭毛——细菌通常有几条从其表面伸出——都逆时针旋转时，它们会形成一个束，像风中编织的辫子一样拖在游泳细胞后面，引导它直线前进。但只要有一个鞭毛马达反转方向开始顺时针旋转，这个束就会散开；反向旋转的丝状体会解开"辫子"，使细胞的鞭毛马达相互冲突，导致细胞四处乱踢。

在伯格的工作之前，"分子马达的想法是疯狂的——不可能有任何东西会旋转，"伯格以前的学生、现在在哈佛大学拥有自己实验室的塞缪尔说。它会摆动，当然，但旋转？"这需要某种几何结构，人们认为生物学无法实现。"

恰恰相反。"生物学可以制造轮子，"塞缪尔说。"现在我们知道。"

过去15年，一种称为冷冻电镜的成像技术的改进，使研究人员能够看到鞭毛马达的组成部分。这阐明了它的工作原理。

马达的基部是"C环"（或"细胞质环"），由34个相同的蛋白质组成的环，漂浮在细胞膜内的细胞质中。科学家们在20世纪80年代和90年代发现，当C环旋转时，鞭毛也随之旋转。但它为何以及如何旋转并不明显。

最近的研究显示，主角是马达的"定子"，这是较小的蛋白质复合体，它们将自己锚定在C环上方和外侧的细胞壁（内膜）上。定子的数量因细菌种类而异（大肠杆菌每个鞭毛有10或12个可用的定子），在特定时间有多少个锁定到C环上取决于细胞的重量或周围流体的粘度。

每个定子由两个中心蛋白质组成，它们从细胞壁悬垂下来，另外五个不同种类的蛋白质围绕这对中心蛋白质形成一个五边形环。这个五边形结构是与C环摩擦接触的部分。

定子的5:2几何结构在2020年通过两项冷冻电镜研究被揭示，一项由牛津大学的苏珊·李及其团队完成，另一项由哥本哈根大学的尼古拉斯·泰勒和柏林洪堡大学的马克·埃哈特领导的团队完成。这一发现提出了关于整个马达如何工作的假设：定子的五边形环旋转，然后带动更大的C环旋转，从而带动整个鞭毛旋转。

每个五边形环像旋转门一样转动，每次转动十分之一圈。推动旋转门通过的是质子流——与原子中带正电的粒子相同。质子会自行流入细胞，原因我稍后会解释。这就是质子动力。

五边形环内两个蛋白质的不对称定位，允许来自细胞外的一个质子与其中一个蛋白质弱结合。当这些蛋白质相互推挤时，质子解离，在此过程中对环施加扭矩。这为另一个中心蛋白质发生相同过程创造了机会。通过这种方式，质子有效地踩踏着鞭毛马达的引擎。每秒有超过2000个质子通过五边形的"旋转门"。2025年12月，塞缪尔发表了一项验证这一点的实验结果。

质子总是想要流入细胞，而不是流出。通过这种方式，它们总是推动五边形环顺时针旋转。通常，这会使C环逆时针旋转（像啮合齿轮的反向转动），从而推动游泳细胞前进。然而，鞭毛马达如何切换方向呢？2024年，另外两项冷冻电镜研究——一项来自当时在美国国立卫生研究院团队的苏珊·李，另一项来自范德比尔特大学的蒂娜·艾弗森领导的团队——揭示了答案。

回想一下，当环境条件似乎恶化时，鞭毛马达会切换方向，导致细菌翻滚。当漂浮进来的营养分子减少时，细菌会"磷酸化"一种叫做CheY的蛋白质，用磷原子标记它们。在几毫秒内，磷酸化的CheY分子在细胞内扩散，其中一个会与一个C环蛋白质结合。这个微小的变化引发了一个转变：该蛋白质翻转为不同的结构构型，进而翻转下一个蛋白质，然后是再下一个。几乎瞬间，整个C环重塑自身，就像一个发夹弹入其两种稳定形式中的另一种。塞缪尔的团队在2026年3月发表的一项研究中证实，该系统对单个信号分子很敏感。

当C环处于其改变后的形状时，定子——那些顺时针旋转的小马达——会与C环的内边缘（而非外边缘）摩擦旋转。结果，C环也顺时针旋转。鞭毛束散开，细胞开始翻滚。

很快，不稳定的磷原子从CheY蛋白质上脱落，导致C环的蛋白质翻回其原始的稳定构型，并再次逆时针旋转。细菌恢复向前运动，朝着新的方向，寻找更多食物。

"这是一种非常优雅的方式，将单向动力转化为大物体的双向旋转，"现在圣裘德儿童研究医院的李说。

驱动鞭毛马达的质子动力是由彼得·米切尔在1961年提出的，他是一位生物化学家，在英国康沃尔郡一个乡村庄园的私人实验室工作。尽管最初遭到否定甚至嘲笑，米切尔后来因其关于质子流不断流入细胞而细胞又积极将其泵出的想法获得了1978年诺贝尔化学奖，并认为这是关键细胞过程背后的驱动力。

质子流入是因为它们从高浓度区域（细胞外）扩散到低浓度区域（细胞内）。一个细菌内部一次只有不到100个自由质子，而周围同等体积的水中则有数万个。细胞通过称为电子传递链的机器来维持这种状态，每秒泵出数千个质子。当质子被泵出时，由于净负电荷以及粒子（此处为质子）在空间中更均匀地扩散导致熵增加的总趋势，成千上万的质子又被吸引流入。细胞已经装配了各种分子机器，它们像河流上的水车一样，利用流入细胞的质子流。

"这超出了人类对事物运作方式的正常理解，"曼森说。"每秒有成千上万的质子进入细胞，而细胞内却只有几十个，这怎么可能？因为它们会结合到某些东西上，然后又被泵出去。平衡过程快得令人难以置信。"

因此，使细胞运转、赋予原子排列以生命的，是高效地移除质子，以便更多的质子流入。"如果你为质子打开一个通道，它们会涌入细胞，质子动力瞬间就会消失，"曼森说。他见过这种情况发生，当细胞饥饿无法泵出足够质子时。电压降至零，细胞的机器停止运转。如果你是一个细菌，你的鞭毛马达就停了。你被困住了。

在我惊叹于鞭毛马达以及转动其齿轮的质子流入时，我很少如此热爱生物学。"质子动力的熵能被转化为旋转的动能，"曼森说。"就是这样。全部就是如此。如果你理解了这一点，你基本上就理解了生物学中所有发生之事的基础。"

英文来源：

What Physical ‘Life Force’ Turns Biology’s Wheels?
Introduction
You’re the earliest known life form. There’s no food around right now. It would be great to go somewhere else. But you’re stuck. Really stuck. At your size (a couple of microns), water feels like tar, or rather, it feels the way being stuck in tar will eventually feel to a human. What do you do?
[One or more billion years later.] You’ve found the perfect solution.
Literally perfect.
“You can assume the system is working optimally,” said Aravinthan Samuel, a biophysicist at Harvard University.
Evolution has created the flagellar motor, a combination propeller/brain that enables single-celled bacteria to move toward food sources. It’s an electric motor that rotates at several hundred revolutions per second — faster than the flywheel in a race car engine — to twirl a tail-like flagellum that pushes the cell along. When the flagellar motor rotates counterclockwise, it propels the cell through the water 10 or more times its own length in a second. The motor can also rotate clockwise, causing the cell to tumble about randomly. This amazing, self-assembling, signal-processing, direction-switching molecular machine is so powerful yet so spare that, billions of years later, it’s still used by bacteria in virtually every gut and puddle on Earth.
Since the discovery of the bacterial flagellar motor in the 1970s, biologists and creationists alike have marveled at its design like medieval architects staring with awe at the dome of the Pantheon built by their Roman ancestors. It’s hard to fathom the level of engineering achievable by a billion years of bacterial evolution, especially with only 20 minutes between cell generations, which allows for a truly astronomical number of mutations and trial runs. Creationists hold up the bacterial flagellar motor as a prime example of intelligent design — specifically the concept of “irreducible complexity,” a biological system so intricate, they say, that it couldn’t possibly have arisen in stages through the gradual, stepwise process of Darwinian evolution.
Over the past few decades, scientists have toiled to unravel how the flagellar motor works — namely, how it rotates and switches directions.
Now they finally have. A wave of studies since 2020 has cracked the molecular structures of the flagellar motor’s parts, including, most importantly, the small cogwheels that turn the larger cogwheel at the flagellum’s base. The final pieces of this dynamic puzzle fell into place as recently as March 2026.
“My lifelong quest is now fulfilled,” said Mike Manson, a professor emeritus of biophysics at Texas A&M University who started studying the flagellar motor in the 1970s. “I finally understand how this thing I’ve been studying for 50 years actually works. That’s about as satisfying as can be.”
The workings of the flagellar motor are ingenious indeed. But when I began interviewing these scientists about what they’ve figured out, I didn’t anticipate that the explanation of the motor would clarify all of biology for someone like me, who seeks mechanistic, physical explanations. The machine, I learned, exploits a driving force I had not known about (though biophysicists have) — the physical “life force” that powers processes in cells. This “proton motive force” doesn’t just turn the cogs of the flagellar motor; it’s the juice we all run on.
The flagellar motor was discovered by the late Howard Berg, an ingenious experimenter who spent most of his career at Harvard. Berg set out in the early 1970s to apply his training in physics to understanding how bacteria move. The problem was that, under a microscope, Escherichia coli, Salmonella, and other motile bacteria almost instantly swam out of frame. So Berg invented and built an automatic tracking microscope that could keep a bacterium in view as it moved around. “What it recorded were all the corrections that had to be made to the microscope stage in order to keep the bacterium in place, and that of course gives you a readout of what the path of the swimming bacterium was,” said Manson, who joined Berg’s project as a postdoc in 1975.
The data revealed that bacteria “run and tumble” — that is, they switch back and forth between swimming straight and rolling around chaotically. Berg theorized that bacteria change their swimming state based on the chemical gradients sensed as they swim. Their default behavior is to swim straight. If the concentration of sugars and other nutrients is increasing, the cell keeps going forward. If the concentration drops, it tumbles; reoriented in a new direction, the bacterium then resumes swimming straight. This process keeps the bacterium in the vicinity of harvestable molecules, which it absorbs through channels in its cell wall and membrane.
Berg guessed that the flagellar motor was a rotor that turned the flagellum like a screw. “He did it by sticking two cells together by their flagella and seeing them spinning in opposite directions from each other,” Manson said. “From that, with no knowledge, he hypothesized that the bacterial flagellum rotates. Way ahead of his time. That was 50 years before understanding how this motor works.”
Further experiments indicated that the flagellar motor also switches direction. When its flagella — bacteria typically have several protruding from their surfaces — are all spinning counterclockwise, they form a bundle that trails behind the swimming cell like a braid in the wind, steering it straight. But as soon as one flagellar motor reverses direction and starts rotating clockwise, the bundle falls apart; the reverse-twirling filament unravels the braid and puts the cell’s flagellar motors at cross-purposes, kicking the cell around.
Before Berg’s work, “the idea of a molecular motor was bonkers — no way anything rotates,” said Samuel, Berg’s former student who now runs a Harvard lab of his own. It could wiggle, sure, but rotate? “It requires a certain geometry that people didn’t think was accessible to biology.”
Au contraire. “Biology can build wheels,” Samuel said. “Now we know.”
Improvements over the last 15 years in an imaging technique called cryo-EM (cryogenic electron microscopy) have enabled researchers to see the flagellar motor’s component parts. That has clarified how it works.
At the base of the motor is the “C ring” (or “cytoplasmic ring”), a ring of 34 identical proteins floating in the cytoplasm within the cell membrane. Scientists in the 1980s and ’90s figured out that when the C ring rotates, the flagellum does too. But why and how it rotates wasn’t obvious.
The stars of the show, recent research showed, are the motor’s “stators,” smaller protein complexes that anchor themselves to the cell wall (an inner membrane) above and outside the C ring. The number of stators varies by bacterial species (E. coli has 10 or 12 available per flagellum), and how many lock into the C ring at a given time depends on the weight of the cell or the viscosity of the surrounding fluid.
Each stator consists of two central proteins that dangle from the cell wall and five proteins of a different kind that form a pentagonal ring around the pair. This pentagonal structure is the part that rubs up against the C ring.
The 5:2 geometry of the stators was revealed in 2020 in a pair of cryo-EM studies, one by Susan Lea and a team at the University of Oxford, and one from a group led by Nicholas Taylor of the University of Copenhagen and Marc Erhardt of Humboldt University of Berlin. The finding pointed to a hypothesis about how the whole motor works: The stators’ pentagonal rings rotate, which then turns the larger C ring, and with it the whole flagellum.
Each pentagonal ring turns like a turnstile, one-tenth of a revolution at a time. What pushes through the turnstile is a stream of protons — the same positively charged particles found in atoms. Protons flow into cells of their own accord, for reasons I’ll get to. This is the proton motive force.
The asymmetric positioning of two proteins inside a pentagonal ring allows a proton from outside the cell to weakly bond to one of them. As the proteins jostle, the proton unbinds, exerting torque on the ring as it goes. That creates an opportunity for the same process to take place with the other central protein. In this way, protons effectively pedal the engine of the flagellar motor. Every second, more than 2,000 of them pass through the pentagonal turnstiles. In December 2025, Samuel published the results of an experiment that verified this.
Protons always want to flow into cells, never out. In passing that way, they always push the pentagonal rings clockwise. Normally, this turns the C ring counterclockwise (like the opposite turning of interlocking gears), which propels the swimming cell forward. How, though, can the flagellar motor switch directions? In 2024, another pair of cryo-EM studies, from Lea, then with a team at the National Institutes of Health, and a group led by Tina Iverson at Vanderbilt University, revealed the answer.
Recall that a flagellar motor switches directions, causing the bacterium to tumble, when environmental conditions seem to be getting worse. When fewer nutritious molecules drift in, the bacterium “phosphorylates” proteins called CheY, tagging them with phosphorus atoms. Within milliseconds, phosphorylated CheY molecules diffuse around the cell, and one of them binds to one of the C-ring proteins. This small change triggers a transformation: The protein flips into a different structural configuration, which flips the next protein, and then the next. Almost instantly the whole C ring reshapes itself, like a hair clip snapping into the other of its two stable forms. Samuel’s team confirmed that the system is sensitive to a single signaling molecule in a study published in March 2026.
While the C ring is in its altered shape, the stators — the little clockwise-revolving motors — rotate against the inner edge of the C ring, rather than its outer edge. As a result, the C ring turns clockwise too. The flagellar bundle falls apart, and the cell tumbles.
Soon enough, the unstable phosphorus atom falls off the CheY protein, causing the proteins of the C ring to flip back to their original stable formation and turn counterclockwise again. The bacterium returns to forward movement, in a new direction, is search of more food.
“It’s a really elegant way of turning a unidirectional power into bidirectional rotation of the large object,” said Lea, who is now at St. Jude Children’s Research Hospital.
The proton motive force that drives the flagellar motor was proposed in 1961 by Peter Mitchell, a biochemist who worked out of his own private lab at a country estate in Cornwall, England. Though initially dismissed and even ridiculed, Mitchell went on to win the 1978 Nobel Prize in Chemistry for his idea that a current of protons constantly flows into the cell as the cell vigorously pumps them back out, and that this is the driving force behind key cellular processes.
Protons flow in because they’re diffusing from an area of high concentration (outside the cell) to an area of low concentration (inside). There are fewer than 100 free protons inside a bacterium at a time, while a similar volume of the surrounding water has tens of thousands. The cell maintains this state with machines called electron transport chains that pump out thousands of protons per second. As protons are pumped out, thousands more flow in, drawn by the net negative electric charge and the general tendency for entropy to rise as particles (in this case, protons) spread out in space ever more evenly. Cells have rigged up all kinds of molecular machines that, like water mills on rivers, take advantage of proton currents coming into the cell.
“It boggles the normal human understanding of how things work,” Manson said. “How can you have thousands and thousands of protons coming into the cell every second and still have only a few dozen inside the cell? Because they bind to something, they get pumped out again. The equilibria are so incredibly fast.”
So what makes the cell go, what breathes life into the atomic arrangements, is the efficient removal of protons so that more protons will flow. “If you were to open up a channel to protons, they would come pouring into the cell, and the proton motive force would be gone instantly,” Manson said. He’s seen this happen, when cells starve and can’t pump enough protons out. The voltage drops to nothing, and the cell’s machinery shuts down. If you’re a bacterium, your flagellar motor stops. You’re stuck.
Rarely have I loved biology more than when marveling at the flagellar motor and the influx of protons that turns its gears. “The entropic energy of the proton motive force gets converted into the kinetic energy of the rotation,” Manson said. “That’s all it is. All of it is just that. If you understand that, you basically understand the underpinnings of all that happens in biology.”