内容来源：https://www.quantamagazine.org/genes-have-harnessed-physics-to-help-grow-living-things-20251010/

内容总结：

【新华社专电】生命形态的塑造不仅受基因指令调控，更与物理力学作用密切相关。近期多项突破性研究表明，胚胎发育、器官形成等关键生物过程背后，存在着不容忽视的物理力学机制。

法国生物物理学家团队三月发现，小鼠胚胎发育中首个体轴（头尾方向）的形成竟与“马兰戈尼效应”这一经典物理现象有关。该效应早于1855年由詹姆斯·汤姆森通过葡萄酒“酒泪”现象首次描述：由于酒精与水表面张力差异，液体会沿杯壁持续循环流动。研究显示，胚胎细胞群通过基因调控产生表面张力差，驱动细胞组织以类似“酒泪”的运动模式流动，最终实现胚胎拉长与体轴确立。

这一发现印证了生物学界日益重视的“力学发育”理论。剑桥大学物理学家亚历山大·卡布拉指出：“物理学与力学机制有助于我们理解组织尺度的生物学现象。”随着现代显微成像技术的突破，科学家得以实时观测细胞运动与组织重构，为力学调控理论提供了直接证据。

力学视角的回归使达西·汤普森1917年著作《生长与形态》重获关注。这位先驱曾强调生物形态与非生命物质在物理规律上的共通性，反对将一切归因于自然选择。如今，其“物理力量塑造生命”的核心观点正获实验验证。

在羽毛发育研究中，洛克菲勒大学团队发现分子信号并非直接指令细胞，而是通过改变组织力学特性，引导毛囊形成。项目负责人罗德里格斯表示：“遗传指令只需提供基础框架，更宏观的力学过程将自发完成复杂形态构建。”

学界普遍认为，基因与物理力学的协同作用将成为发育生物学新范式。正如卡布拉所总结：“凡有运动之处，必有力学参与。生命创造的奥秘正存在于基因编码与物理规律的握手之中。”

中文翻译：

基因如何运用物理学塑造生命形态

轻抿一口葡萄酒，你会注意到液体沿着湿润的杯壁不断向下流淌。1855年，开尔文勋爵的兄长詹姆斯·汤姆森在《哲学杂志》上阐释了这些酒"泪"或"酒腿"现象源于酒精与水表面张力的差异。汤姆森写道："这一事实解释了几种非常奇特的运动现象。"他未曾意识到，这种后来被命名为马兰戈尼效应的现象，竟可能影响着胚胎的发育方式。

今年三月，法国生物物理学家团队报告称，当均质细胞团开始伸长并形成头尾轴——生物体首个决定性特征时，这一关键转变正是由马兰戈尼效应主导。

该发现颠覆了生物学传统认知范式。通常生物学家将生长、发育等过程归因于基因指令触发的化学信号，但这种解释往往存在缺失。如今研究者日益重视机械力在生物学中的作用：这些力根据组织材料特性进行推拉，以基因无法实现的方式引导着生长发育。

现代成像与测量技术通过海量数据为力学解释提供了可能，开启了科学家的新视野。"过去几十年的变革在于我们能实时观察生命活动，从细胞运动、细胞重组到组织生长的力学机制，"近期研究的核心成员、艾克斯-马赛大学的皮埃尔-弗朗索瓦·莱纳表示。

这种向力学解释的转向使前基因时代的生物学模型重获关注。例如1917年，苏格兰生物学家达西·汤普森出版《生长与形态》，揭示了生物形态与非生命物质形态的相似性。该书旨在纠正当时过度依赖达尔文自然选择解释万物的倾向。他提出的"物理学同样塑造生命"的论点正重新流行。

"我们的假说是：物理学和力学能帮助理解组织尺度的生物学现象，"剑桥大学物理学家亚历山大·卡布拉指出。当前要务是解析基因与物理学如何协同塑造生物体。

流动中的生长密码

胚胎与组织生长的力学模型并非新概念，但生物学家长期缺乏验证手段。胚胎本身难以观测——它们体积微小且透光性差，如同磨砂玻璃般散射光线。新型显微镜与图像分析技术终于为发育过程打开了清晰窗口。

莱纳团队运用新技术观测小鼠原肠胚模型（模拟胚胎早期发育的干细胞团）内部的细胞运动，发现细胞沿模型边缘上涌，继而形成组织流向下回流。这让莱纳联想到液滴运动，在查阅液滴表面张力文献时，他灵光乍现地联系到马兰戈尼效应。

詹姆斯·汤姆森早年的描述揭示：当两种表面张力不同的液体相遇，较高者会牵引较低者。酒杯中酒精从湿润杯壁快速蒸发，留下表面张力更高的水相，从而将酒液牵引至湿润区顶端，最终因重力形成"酒泪"。这种循环流动与原肠胚中的组织流动如出一辙。研究团队通过马兰戈尼型组织流模型验证，发现实验数据与预测高度吻合。

马兰戈尼流虽是力学效应，但基因通过调控表面张力差异参与其中：初始阶段基因在细胞团特定区域高浓度表达两种蛋白质，这些蛋白导致局部表面张力降低，驱使组织流远离该区域。组织沿原肠胚外围流动后回旋至中心——恰似酒泪沿杯壁回滴。这个过程促使原肠胚伸长。卡布拉评价："这完美展现了力学与分子细胞生物学内在复杂性如何协同塑造生物体。"

羽序生成的力学密码

2017年，洛克菲勒大学形态发生实验室的艾伦·罗德里格斯与艾米·夏尔遭遇研究困境。他们试图破解鸟类羽毛规则间距的成因，当时主流理论认为鸟胚皮肤组织会分泌特殊形态发生素，引导基因在特定位置产生毛囊蛋白。但研究者始终找不到启动该过程的遗传信号。

他们开始怀疑力学张力扮演重要角色。2023年《科学》期刊的论文中，团队发现形态发生素确实在羽囊开始萌芽前分泌，但它们并非直接影响单个细胞，而是作用于更大尺度的组织区域。形态发生素通过改变组织材料特性，为力学推动实现毛囊图式奠定基础。

"最令人惊叹的是，遗传和分子层面仅需提供相对简单的指令，"罗德里格斯解释，"因为其他层级会涌现出额外的过程与特性。"对他而言，核心问题在于基因-细胞-组织等多尺度过程中各种机制如何协同。禽类羽囊发育案例中，分子与组织层级的变化是同步涌现的。这项研究"挑战了生物学主流观点——即调控机制源于分子层面，而后自下而上决定宏观形态"。

蛋白质的力学之舞

某些蛋白质确实能改变单个细胞的材料特性，为微观层面的力学作用搭建舞台。例如果蝇胚胎发生时，卡布拉团队发现细胞不仅重新排列，更会发生拉伸。这种拉伸行为似乎直接源于基因活动导致的特殊细胞弹性。

普通弹簧或橡皮筋遵循胡克定律：伸长量与外力成正比。但若拉伸对象处于粘性流体中，延伸量则与时间相关（如搅拌糖浆时，快速搅拌会受阻）。生物体同样存在这种时间依赖性。多个团队检测果蝇胚胎细胞拉伸时，发现其延伸量与受力时间的平方根成正比。关键问题在于：这种行为从何而来？

六月《物理评论快报》的论文中，康斯坦丁·杜布罗温斯基团队用细胞中最丰富的肌动蛋白作出解释：肌动蛋白丝在合成时如同弹簧般牵引细胞，产生抵抗拉伸的阻力，从而形成观测到的现象。团队通过抑制肌动蛋白组装的对照实验验证该机制，"本质上，弹性响应几乎完全消失"。

卡布拉指出，尽管该研究论证有力，但关于拉伸行为的讨论仍在继续。生物学面临的挑战在于厘清现象间的因果关系，判断特定因素是变革的主导力量、辅助因素还是无足轻重的副产品。

这些争论与百年前达西·汤普森记录的几何相似性之辩遥相呼应。但他关于"几何形态源于底层物理力"的核心论点，正经受住现代科学的检验。"对我们许多人而言，"卡布拉总结道，"有运动之处必有力学参与，这再自然不过。"

英文来源：

Genes Have Harnessed Physics to Help Grow Living Things
Sip a glass of wine, and you will notice liquid continuously weeping down the wetted side of the glass. In 1855, James Thomson, brother of Lord Kelvin, explained in the Philosophical Magazine that these wine “tears” or “legs” result from the difference in surface tension between alcohol and water. “This fact affords an explanation of several very curious motions,” Thomson wrote. Little did he realize that the same effect, later named the Marangoni effect, might also shape how embryos develop.
In March, a group of biophysicists in France reported that the Marangoni effect is responsible for the pivotal moment when a homogeneous blob of cells elongates and develops a head-and-tail axis — the first defining features of the organism it will become.
The finding is part of a trend that defies the norm in biology. Typically, biologists try to characterize growth, development and other biological processes as the result of chemical cues triggered by genetic instructions. But that picture has often seemed incomplete. Researchers now increasingly appreciate the role of mechanical forces in biology: forces that push and pull tissues in response to their material properties, steering growth and development in ways that genes cannot.
Modern imaging and measurement techniques have opened scientists’ eyes to these forces by flooding the field with data that invites mechanical interpretations. “What has changed over the past decades is really the possibility to watch what happens live, and to see the mechanics in terms of cell movement, cell rearrangement, tissue growth,” said Pierre-François Lenne of Aix Marseille University, one of the researchers behind the recent study.
The shift toward mechanical explanations has revived interest in pre-genetic models of biology. For example, in 1917 the Scottish biologist, mathematician and classics scholar D’Arcy Thompson published On Growth and Form, which highlighted similarities between the shapes found among living organisms and those that emerge in nonliving matter. Thompson wrote the book as an antidote to what he thought was an excessive tendency to explain everything in terms of Darwinian natural selection. His thesis — that physics, too, shapes us — is coming back into vogue.
“The hypothesis is that physics and mechanics can help us understand the biology at the tissue scale,” said Alexandre Kabla, a physicist and engineer at the University of Cambridge.
The task now is to understand the interplay of causes, where genes and physics somehow act hand in hand to sculpt organisms.
Grow With the Flow
Mechanical models of embryo and tissue growth are not new, but biologists long lacked ways of testing these ideas. Just seeing embryos is difficult; they are small and diffusive, bouncing light in all directions like frosted glass. But new microscopy and image analysis techniques have opened a clearer window on development.
Lenne and his co-workers applied some of the new techniques to observe the motion of cells inside mouse gastruloids: bundles of stem cells that, as they grow, mimic the early stages of embryo growth.
Courtesy of Pierre Francois Lenne
Their observations revealed that cells flow up the sides of the gastruloid, then form a stream of tissue flowing down the middle. For Lenne, the system brought to mind a droplet, and on reviewing the literature on the surface tension in a moving droplet, he hit upon the Marangoni effect.
James Thomson’s 1855 description of the Marangoni effect explained how, when two liquids that have different surface tensions meet, the fluid with the higher surface tension will pull on the other. This happens because surface tension is just the tendency of the outermost molecules in a fluid to be drawn inward by neighboring molecules. When two fluids meet, the higher-tension fluid will have a stronger pull, so the lower-tension fluid will move in the higher-tension fluid’s direction. In a wineglass, the alcohol on the wetted sides of the glass evaporates quickly, leaving a more watery liquid behind. Water has a higher surface tension than alcohol, so the watery sides drag the wine in the glass up to the top of the wetted area. It eventually drips down under its own weight, forming “tears.”
This flow of the wine up the sides and down again is similar to the flow of the tissue in the gastruloid. Indeed, when the team tested a model of Marangoni-type gastruloid tissue flow, they found what they considered a striking fit with their experimental data.
Mark Belan/Quanta Magazine; Source: Pierre-François Lenne
The Marangoni flow is a mechanical effect, but genes are involved too: They set up the surface tension difference. At first, genes produce a higher concentration of two particular proteins in one part of the blob of cells. These proteins lead to lower surface tension, and so tissue flows away from that region. The tissue moves around the periphery of the gastruloid before recirculating down its center — just as wine tears drip back down the side of a glass. The process elongates the gastruloid. It’s “a very nice example of how mechanics, coupled with all the intrinsic complexity of molecular and cellular biology, has a very important role in shaping organisms,” Kabla said.
Scales of a Feather
In 2017, Alan Rodrigues and Amy Shyer couldn’t find what they were looking for. The pair, co-leaders of Rockefeller University’s Laboratory of Morphogenesis, had been trying to figure out how the regular spacing of a bird’s feathers comes about. The popular theory at the time was that bird embryos secrete special molecules called morphogens across their skin tissues. These morphogens would then prompt genes to produce proteins at the right places to form follicles. But the researchers couldn’t find any genetic signal that would start the process.
They came to suspect that mechanical and tensile forces were playing a significant role. In a 2023 report in Science, their team found that morphogens were indeed secreted just before a feather follicle started to bud. But the morphogens didn’t seem to be influencing development on the level of individual cells. Instead, they were influencing larger swaths of tissue. The morphogens affected the tissue’s material properties, setting the stage for mechanical forces to push and pull on the tissue for follicle patterning.
“What’s really amazed us is that you might be able to get by with a relatively simple amount of instruction from the genetic and molecular level,” said Rodrigues. “Because you have additional emergent processes and properties happening at other levels.”
For Rodrigues, the big issue is how the various processes work together across length scales, from genes to cells to tissues. It’s not that everything starts on the smallest scales and builds from there. In the case of avian feather follicle development, changes at the molecular and tissue levels emerge together. The work “challenges the general view across much of biology,” Rodrigues said, “that regulation or causation emerges at the molecular level and then feeds upward across scales to dictate high-level properties such as form.”
Springing Into Action
Some proteins do affect material properties within individual cells, setting the stage for mechanical forces to act at that level too. For instance, during the embryogenesis of a fruit fly, cells in the embryo don’t just rearrange themselves; Kabla and his co-authors discovered that the cells also stretch. This stretching appears to be directly attributable to gene activity that results in a curious characteristic of the cells’ stretchiness.
Take a spring or an elastic material like a rubber band, and the material will extend in proportion to the force applied. This relationship is known as Hooke’s law, and it holds quite generally. Unless, that is, the object being stretched is in some kind of viscous fluid, in which case the amount of extension also depends on time. (Think of stirring molasses: It’s hard to stir fast.)
Public Domain
Biological organisms appear to share this dependence on time. Several groups have measured the stretching of certain cells in the fruit fly embryo and found that their extension depends on the square root of the amount of time the force is applied. The question then becomes: Where does this behavior come from?
In a paper in Physical Review Letters in June, Konstantin Doubrovinski and colleagues at the University of Texas Southwestern Medical Center explain it in terms of the production of actin, one of the most abundant proteins in these cells. They suggest that the actin filaments effectively pull on the cell like springs as they are produced, creating resistance to the force that stretches the cells and giving rise to the observed behavior.
Doubrovinski and his team verified the role of actin by repeating the experiment using drugs that prevent the actin protein from assembling. “Essentially, the elastic response more or less completely goes away,” he said.
Kabla says that while the study makes a strong case, discussion of the stretching behavior continues. One of the challenges facing biology, he points out, is figuring out what is causing what, and whether a given phenomenon is a key driver of change, a contributing factor, or an unimportant consequence.
These questions echo similar debates over the biological significance of the geometric similarities D’Arcy Thompson cataloged more than 100 years ago. But Thompson’s central argument that these geometric forms result from underlying physical forces is standing up to modern scrutiny.
“To many of us,” Kabla said, “it seems natural that where there’s motion, mechanics is likely to be involved.”