内容来源：https://www.quantamagazine.org/how-spiders-spin-silk-dope-into-natures-toughest-material-20261028/

内容总结：

科学家揭秘蜘蛛如何将“丝浆”纺成自然界最强韧材料

蜘蛛从墙上跌落时不会坠落很久。在毫秒之间，它就能将一种蛋白质混合液纺成坚固的攀爬工具，借助一根纤细闪亮的丝线将自己拉回原处。这种丝线比凯夫拉纤维更坚韧，比钢铁更坚固，且具有柔韧性并与人体生物相容。科学家一直梦想将蜘蛛丝制成高性能材料，用于安全带、头盔、海军装备，甚至用于修复脑细胞的支架。但实验室仿制蜘蛛丝的尝试始终未能达到天然丝的水平，原因在于研究人员对蜘蛛如何将丝腺中的“丝浆”——一种蛋白质、水和盐的液体混合物——纺成非凡固体的过程了解不足。

圣迭戈州立大学化学家和光谱学家格雷戈里·霍兰德表示，绘制这一过程背后的分子机制是该领域“真正的圣杯”。他领导的最新研究描述了液体丝浆中的分子如何在转化为固体丝纤维之前，重组为被称为凝聚体的半液体液滴。这一成果提供了对蜘蛛“丝工厂”的原子级观察。

研究结果也为凝聚体的形成提供了实用指南。自然界反复利用凝聚体来组织分子，以完成遗传过程并制造出强度惊人的生物材料。未参与该研究的麦吉尔大学生物材料科学家马修·哈林顿表示：“越来越清楚的是，凝聚体是广泛生物体中普遍使用的策略。”通过揭示自然界如何利用凝聚体，科学家希望再造出一些最坚固的材料。

蜘蛛是令人惊叹的天然工厂，能纺出多达七种丝，同一种蜘蛛往往能纺出其中多种。包裹猎物以备日后进食的囊状丝、吸收冲击的橡胶状鞭毛丝、将蛛网和蜘蛛固定在墙面上的拖曳丝——每种丝的性質因物种而异，并与其分子组装方式相关。

1907年，科学家发现蜘蛛丝由长模块化蛋白质构成，后来被命名为蛛丝蛋白。蜘蛛丝由嵌入非结晶基质的扁平蛋白质片层（β折叠）构成。本世纪初，研究人员在溶液中观察蛛丝蛋白时，未发现大多数蛋白质中那种有序的固定结构，而是看到内部无序区域不断飘动、形成并重新形成各种形状。此后，研究人员开始探究这种无序蛋白质混合物如何组织成坚固的固体纤维。

早期理论认为丝浆中的蛋白质像晶体一样开始相互排列，同时保持动态，处于“液晶”过渡态。另有理论认为蜘蛛丝类似蚕丝，蛋白质组织成胶束，再压缩成丝纤维。2007年，研究人员注意到实验室工程化的蛛丝蛋白形成了液状球体。2009年，科学家在受精线虫卵中发现聚集RNA分子的液滴，即凝聚体。研究人员意识到凝聚体浓缩分子，将其预组织成灵活的微环境，而不像固体那样将分子锁定在位。哈林顿说：“因为它们是流体，所以具有可塑性，生物可以将其塑造成想要的任何形状。”

更多研究表明，活细胞广泛利用凝聚体来组织DNA、调控基因表达和包装蛋白质。在宏观尺度上，它们帮助物种构建有趣的材料——塑造鱿鱼喙的硬度梯度、形成贻贝附着岩石的强力黏合剂，以及沙堡蠕虫建造保护管的海洋水泥。霍兰德说：“这一直是生物学中的热门领域。”

尽管研究人员十多年前就描述过实验室制造的蛛丝蛋白中形成凝聚体样球体，但直到2020年京都大学生物材料化学家沼田圭司提出蜘蛛丝在从液体丝浆向固体丝线转变过程中经历凝聚体阶段，这些结构才被视为凝聚体。凝聚体通过“液-液相分离”形成，即液体中的分子在pH值、化学物质或温度变化等刺激下开始弱相互作用，容易成键和断键。沼田提出，丝腺中部壶腹中的磷酸盐可能引发这些相互作用。但在霍兰德实验室当时的研究生汉娜·约翰逊决定深入研究之前，尚无人描述驱动凝聚体形成的原子级机制。

2023年和2024年期间，每隔几个月就有一批雌性黑寡妇蜘蛛送达圣迭戈州立大学化学系。这些蜘蛛的拖曳丝蛛丝蛋白是全蜘蛛中表征最充分的之一，且全年可得。在两周期内，约翰逊六次戴上双层防护手套，与几名学生一起对经二氧化碳麻醉的蜘蛛进行“取丝”。他们用镊子从蜘蛛纺器轻轻拉出丝线，绕在由旋转马达驱动的瓶子上收集。研究人员给黑寡妇喂食富含特定同位素的氨基酸混合物，以便在实验室中检测。

核磁共振波谱可绘制分子结构。约翰逊对液体丝浆及从壶腹收集的凝聚体使用核磁共振，同时实验室博士后凯文·查莱克绘制了固体纤维中蛋白质的原子结构。查莱克说：“我们试图弥合蛋白质在蜘蛛体内和体外所发生的变化之间的差距。同样的蛋白质，为何差异如此之大？两者之间究竟发生了什么？”

约翰逊观察到，向液体丝浆中加入磷酸盐启动凝聚过程后，蛛丝蛋白内在无序区域中精氨酸和酪氨酸两种氨基酸的侧基开始弱相互作用，置换水分，将无序蛋白质组织成更致密的凝胶状凝聚体。这种相互作用在固体纤维中持续存在，表明这些氨基酸充当“分子胶水”，引导无序蛋白质进入凝聚体并最终形成纤维。团队其他成员使用AlphaFold和分子动力学软件进行计算机预测，模拟显示这些氨基酸正好排列在β折叠的弯折处，暗示它们帮助引导蛛丝蛋白进入最终结构。

谢菲尔德大学生物学家克里斯·霍兰德（与格雷戈里·霍兰德无亲属关系）评价说：“理解这些侧基如何相互作用并发展出超越各部分之和的结构，非常精彩。”而且他们使用的是真实蜘蛛而非合成丝，“这非常出色”。新加坡国立大学生物学家杨代文表示，这些发现是凝聚体可由天然丝形成的“直接证据”，“相当重要”。

格雷戈里·霍兰德此前已证明天然蜘蛛丝中存在胶束，他提出胶束、凝聚体和液晶可能是同一相变的三个阶段。液体丝浆中形成的胶束防止无序蛋白质聚结纠缠；蛋白质也可预组装成凝聚体或在释放前排列成液晶状结构。但实际过程可能比顺序进行“更加动态和异质”，多种结构同时在混合物中形成。哈林顿同意这一观点：“我认为这些并不互斥，不同阶段可能发生不同类型的相变。”

然而，关于这些相互作用如何在“工厂流水线”上累积，仍有更多待解之谜。可能还有其他重要的氨基酸相互作用尚未详细绘制，研究人员也希望寻找磷酸盐之外的触发因素。克里斯·霍兰德说：“可能还有一系列其他因素驱动这些蛋白质的结构变化，我们尚未完全了解所有开关。”

完整描述复杂的纺丝过程需要大量努力，但回报可能巨大。与蚕不同，蜘蛛产丝量少且同类相食，难以大规模养殖。在实验室生产蜘蛛丝可能带来新型强韧灵活材料。哈林顿说：“蜘蛛或贻贝这样的生物基本上是在海水或普通空气的环境条件下制造出更优质的材料。”人类尚未掌握模仿这些生物的能力。查莱克说：“有些东西我们也在努力模仿。”他认为额外的强度必定来自β折叠之外的某些结构因素，或来自合成丝方案中常被省略的蛛丝蛋白部分。克里斯·霍兰德说：“我认为一旦真正理解了这些蓝图，我们就能用丝做更多事情。”

中文翻译：

蜘蛛如何将“丝浆”纺成自然界最坚韧的材料

引言

一只蜘蛛从墙上被弹落时，并不会坠落太久。在几毫秒之内，它便将一锅蛋白质纺成坚固的攀爬绳索。借助一根纤细闪亮的丝线，蜘蛛将自己拉回原处。

这种丝线比凯夫拉——用于自行车轮胎和防弹衣的合成纤维——更坚韧，也比钢铁更强。它柔韧且与人体生物相容。科学家梦想将蜘蛛丝制成高性能材料，用于安全带、头盔、海军装备，甚至用于修复脑细胞的支架。但实验室中制造蜘蛛丝的尝试一直不尽如人意，因为研究人员对蜘蛛如何从其丝腺中将“丝浆”——一种蛋白质、水和盐的液体混合物——纺成非凡固体的过程了解得还不够充分。

圣迭戈州立大学的化学家和光谱学家格雷戈里·霍兰德表示，绘制这一过程背后的分子机制图谱是该领域“真正的圣杯”。最近，他领导的研究描述了液态蜘蛛丝浆中的分子如何在转变为固态丝纤维之前，重新组织成被称为凝聚体的半液体液滴。这一成果让我们得以从原子层面窥探蜘蛛的制丝工厂。

这些发现也为凝聚体的形成提供了实用指南。自然界反复利用凝聚体来组织分子，以完成遗传过程并制造出令人惊叹的强韧生物材料。

麦吉尔大学的生物材料科学家马修·哈林顿（未参与该项研究）表示：“越来越清楚的是，凝聚体是各类不同生物体普遍采用的一种策略。”通过揭示自然界如何利用凝聚体，科学家希望重新制造出一些最坚固的材料。

制丝工厂

蜘蛛是不可思议的天然工厂。它们最多能纺出七种丝，而且同一只蜘蛛通常能纺出其中好几种。葡萄状腺丝将昆虫包裹起来以备日后食用。橡胶状的鞭状腺丝加固捕获螺旋，以吸收冲击。拖牵丝将蛛网和蜘蛛固定在墙壁上。每种丝的特性因物种而异，并与其分子的组装方式有关。同一类型的丝在不同物种中也可能具有略微不同的特性。

1907年，科学家发现蜘蛛丝由长条形模块化蛋白质构成，后来被命名为蛛丝蛋白，它们与胶原蛋白和角蛋白同属纤维蛋白家族。半个多世纪后，X射线开始揭示这种纤维的基本结构。蜘蛛丝由扁平的蛋白质片层（称为β折叠）构成，这些片层嵌入在较无序的非晶基质中。

21世纪初，研究人员在检查溶液中的蛛丝蛋白时，并未看到大多数蛋白质中那种有序的固定结构。相反，蛛丝蛋白具有内在无序区域，这些区域不断飘动，形成并重新形成各种形状。研究人员随后开始揭示这锅无序蛋白质如何组织成坚固的固态纤维。

一种早期理论认为，丝浆中的蛋白质开始像晶体一样彼此排列对齐，同时保持动态，处于一种被称为“液晶”的过渡状态。另一种理论认为蜘蛛丝类似蚕丝，其蛋白质组织成胶束（即小球体），然后压缩成丝纤维。

后来，在2007年，研究人员注意到实验室中工程化的蛛丝蛋白形成了液状小球。不久，这类结构在现代生物学中变得无处不在。2009年，马萨诸塞州海洋生物实验室和德国马克斯·普朗克研究所的科学家在受精蠕虫卵中发现了聚集RNA分子的液滴。这些就是凝聚体——悬浮在溶液中的浓缩蛋白质的液体或凝胶状气泡。尽管凝聚体已被观察了一个多世纪，但人们开始将其视为生命活动中分子过程的关键组织工具。

研究人员意识到，凝聚体浓缩分子，将它们预先组织成一个灵活的微环境，而不像固体那样将它们锁定在固定位置。哈林顿说：“因为它们是流动的，所以具有可塑性，因此你（即生物学）可以将它们塑造成任何你想要的形状。”

更多研究表明，活细胞到处都在使用凝聚体，用于组织DNA、调控基因表达和包装蛋白质。在宏观尺度上，它们帮助物种构建有趣的材料。它们帮助将鱿鱼喙塑造成硬度渐变的部件。它们形成强力黏合剂，使贻贝能够附着在岩石上，还形成海洋水泥，沙堡蠕虫用其建造保护管。

霍兰德说：“这一直是生物学中的热门领域。”

尽管研究人员早在十多年前就描述了实验室制造的蛛丝蛋白中形成类似凝聚体的小球，但直到2020年，京都大学的生物材料化学家沼田圭司提出蜘蛛丝在从液态丝浆转变为固态丝线的过程中经历了凝聚体阶段，这些小球才被视为凝聚体。

凝聚体通过“液-液相分离”形成。在这一过程中，液体中的分子在pH值、化学物质或温度变化等刺激作用下，开始彼此发生弱相互作用，容易形成键也容易断裂。沼田提出，蜘蛛丝腺中部（壶腹部）的磷酸盐可能引发这些相互作用。但在霍兰德实验室当时的研究生汉娜·约翰逊决定一探究竟之前，尚无人描述驱动凝聚体形成的原子级机制。

黑寡妇蜘蛛内部探秘

2023年和2024年期间，每隔几个月就有一包雌性黑寡妇蜘蛛抵达圣迭戈州立大学化学系。这些蛛形纲动物通体乌黑，点缀着一抹红色，培育着一种对人类可能造成疼痛的强力毒液。除了这点小麻烦之外，它们是研究蜘蛛丝的良好对象。它们的拖牵丝蛛丝蛋白是所有蜘蛛中表征最充分的之一。而且它们全年可得，不像某些蜘蛛只在特定季节结网。

在两周内共六次，约翰逊戴上两副防护手套。在一个小时的过程中，她和几名学生对被二氧化碳麻醉的黑寡妇蜘蛛进行“取丝”。科学家用镊子轻轻从蜘蛛的纺器——纤维从腹部伸出的喷口——拉出丝线，并通过缠绕在装有旋转马达的小瓶上来卷取。

约翰逊说：“产丝量大的蜘蛛是我们的最爱，但我对那些不愿配合的叛逆者也情有独钟。”在整个过程中，研究人员给黑寡妇蜘蛛喂食一种氨基酸混合物（约翰逊称之为“蛋白质奶昔”），其中富含他们可以在实验室中检测到的特定同位素。

核磁共振波谱法可以绘制分子的结构图。它发出射频扰动原子内部的原子核，原子核随之以该元素特有的方式运动。约翰逊对液态蜘蛛丝浆以及从蜘蛛壶腹部收集的凝聚体使用了核磁共振。与此同时，霍兰德实验室当时的博士后研究员凯文·查莱克（现为加州大学洛杉矶分校研究员）绘制了固态纤维中蛋白质的原子结构。

查莱克说：“我们试图弥合蛋白质在蜘蛛体内和体外时所发生的变化之间的差距。这些是同样的蛋白质，它们怎么会如此不同？两者之间到底发生了什么？”

约翰逊观察到，当她向液态丝浆中加入磷酸盐以启动凝聚过程后，蛛丝蛋白内在无序区域中两个氨基酸（精氨酸和酪氨酸）的侧基开始彼此发生弱相互作用。这种相互作用排出了水，将无序蛋白质组织成更致密的凝胶状材料——凝聚体。这种相互作用在固态纤维中持续存在，表明这些氨基酸充当“分子胶水”，引导无序蛋白质进入凝聚体并最终形成纤维。

团队中的其他人使用AlphaFold（一种建模蛋白质结构的人工智能工具）和分子动力学软件来通过计算预测这一过程。研究人员知道蜘蛛丝的强度来自最终纤维中坚固的β折叠蛋白质结构。团队的模拟显示，这些氨基酸恰好排列在β折叠的弯折处，表明它们有助于引导蛛丝蛋白进入最终结构。

谢菲尔德大学的生物学家克里斯·霍兰德（未参与该研究，与格雷戈里·霍兰德无亲属关系）说：“理解这些侧基如何相互作用，以及它们如何形成大于各部分之和的结构……非常精彩。”而且他们使用的是真实的蜘蛛而非合成丝，“这非常出色。”

新加坡国立大学的生物学家杨代文（未参与该研究）表示，他们的发现是凝聚体可以从天然蛛丝中形成的“直接证据”，这“相当重要”。

他们对凝聚体的描述并不排除此前关于蜘蛛丝形成的理论。格雷戈里·霍兰德此前已证明天然蜘蛛丝中存在胶束，他提出胶束、凝聚体和液晶这三者可能都是同一相变的不同阶段。液态丝浆中形成的胶束防止杂乱无序的蛋白质聚集和缠绕。蛋白质也可以预先组装成凝聚体，或在从纺器释放为高度有序的纤维之前排列成液晶等结构。但格雷戈里·霍兰德表示，实际过程可能比顺序进行“更加动态和异质”，其中几种结构同时在混合物中形成。

哈林顿对此表示认同。他说：“我认为这些并不互相排斥。在不同加工阶段可能发生不同类型的相变。”

尽管如此，关于这些相互作用在这条工厂流水线上如何叠加，还有更多需要了解的地方。研究人员可能尚未详细绘制出其他重要的氨基酸相互作用。他们还想寻找磷酸盐之外启动这一过程的触发因素。克里斯·霍兰德说：“可能还有一系列其他因素在驱动这些蛋白质的结构变化。我们还没有完全弄清所有的开关。”

卓越材料

完整描述错综复杂的纺丝过程需要大量努力，但回报可能是巨大的。与蚕相比，蜘蛛产生的可用丝量很少。蚕已被人类饲养了四千多年以获取蚕茧。制造一件丝绸衬衫需要数千只蚕；而需要大约一百万只蜘蛛，部分原因是它们不产生易于加工的蚕茧。还有一个更实际的原因：它们的同类相食本性使它们难以饲养，因为每只蜘蛛都需要自己的容器。

在实验室中生产蜘蛛丝可能带来一系列新型强韧而柔韧的材料。凯夫拉是一种合成纤维，目前是我们最坚韧的材料，但它需要在非常高的温度和酸性条件下加工。哈林顿说：“而在这里，像蜘蛛或贻贝这样的生物体，基本上是在海水或普通空气的环境条件下制造出更优越的材料。”

人类尚未弄清楚如何与这些生物体匹敌。当科学家在实验室中使用精确的氨基酸序列合成蛛丝蛋白时，所得的丝不如天然丝强壮。查莱克说：“那里发生了什么我们也在努力模仿的事情。”他认为额外的强度一定来自β折叠之外的某种东西，源于丝结构的其他方面，或者来自合成丝溶液中经常被省略的蛛丝蛋白的某些部分。

克里斯·霍兰德说：“我认为一旦我们真正理解了那些蓝图，我们就能用丝做更多的事情。”

英文来源：

How Spiders Spin ‘Silk Dope’ Into Nature’s Toughest Material
Introduction
A spider, when knocked off a wall, doesn’t fall for long. Within milliseconds, it spins a soup of proteins into sturdy climbing gear. Using a thin, shimmering strand of silk, the spider hauls itself back up.
The strand is tougher than Kevlar, the synthetic fiber in bike tires and bulletproof vests, and stronger than steel. It’s flexible and biocompatible with human bodies. Scientists dream of making spider silk into high-performing materials for seat belts, helmets, naval materials, and even scaffolds to help repair brain cells. But attempts to make spider silk in the lab have fallen short because researchers don’t know enough about how a spider spins “silk dope,” a liquid blend of proteins, water, and salt, from its silk glands into a remarkable solid.
Mapping out the molecular mechanisms behind the process is “really the holy grail” for the field, said Gregory Holland, a chemist and spectroscopist at San Diego State University. Recently, he led research that described how the molecules in liquid spider dope reorganize into semiliquid droplets called condensates before turning into solid silk fiber. The result is an atomic-level look into the spider’s silk factory.
The findings are also a practical guide to the formation of condensates, which nature has used repeatedly to organize molecules for genetic processes and for the creation of impressively strong biological materials.
“It’s becoming clear that [condensates are] a common strategy that’s being used across a range of different organisms,” said Matthew Harrington, a biological materials scientist at McGill University who was not involved in the study. By unpacking how nature uses condensates, scientists hope to re-create some of its most rugged materials.
Silk Factory
Spiders are incredible natural factories. They can spin up to seven types of silks, and the same spider can often spin several of them. Aciniform silk wraps up insects for later snacking. Rubbery flagelliform silk reinforces the capture spiral to absorb shock. Dragline silk anchors webs and spiders to walls. Each type of silk has different properties depending on the species and related to how its molecules are assembled. And silks of the same type can have slightly different properties depending on the species.
In 1907, scientists discovered that spider silk is made of long, modular proteins, later named spidroins, which are in the same group of fiber proteins as collagen and keratin. More than half a century later, X-rays started to reveal the fiber’s underlying structure. The silk is made of flat sheets of protein, known as beta sheets, that are embedded in a less ordered, non-crystalline matrix.
In the early 2000s, as they inspected the spidroins in solution, researchers didn’t see organized, fixed structures like those seen in most proteins. Instead, the spidroins featured intrinsically disordered regions that fluttered around, forming and re-forming various shapes. Researchers then started to untangle how this soup of unstructured proteins could organize into strong, solid fibers.
One early theory suggested that proteins in the dope start to align with one another, as in a crystal, while remaining dynamic, in a transitional state known as “liquid crystal.” Another considered spider silk to be like silkworm silk, which has proteins organized into micelles, or small spheres, which then compress into silk fiber.
Then, in 2007, researchers noted that spidroins engineered in the lab formed liquidlike globs. Soon these kinds of structures would become inescapable in modern biology. In 2009, scientists at the Marine Biological Laboratory in Massachusetts and the Max Planck Institute in Germany discovered droplets of aggregated RNA molecules in fertilized worm eggs. These were condensates — liquid- or gel-like bubbles of concentrated proteins suspended in solution. Though observed for more than a century, condensates started to be seen as a critical organizational tool for molecular processes across life.
The researchers realized that condensates concentrate molecules, pre-organizing them into a flexible microenvironment without locking them in place like a solid. “Because they’re fluid, they’re malleable,” Harrington said, “so you [i.e., biology] can kind of shape them into whatever you want.”
Konrad Wothe/NaturePL/Science Source
More research showed that living cells use condensates everywhere, to organize DNA, regulate gene expression, and package proteins. At a macro scale, they help species build interesting materials. They help mold squid beaks into a gradient of stiff parts. They form strong adhesives that allow mussels to attach themselves to rocks, and marine cement that sandcastle worms use to build protective tubes.
“It’s been a hot area in biology,” Holland said.
Though researchers had described condensate-like blobs forming in lab-made spidroins more than a decade earlier, they weren’t thought of as condensates until 2020, when Keiji Numata, a biomaterials chemist at Kyoto University, suggested that spider silk undergoes a condensate phase during its transition from liquid dope to solid thread.
Condensates form by “liquid-liquid phase separation,” a process through which molecules in a liquid can start to interact weakly with one another, easily forming bonds and breaking them, as a result of a stimulus such as a change in pH, chemicals, or temperature. Numata proposed that phosphate in the ampulla, the middle section of a spider’s silk glands, might initiate these interactions. But no one had described the atomic-scale mechanisms that drive their formation until Hannah Johnson, then a graduate student in Holland’s lab, decided to take a look.
Inside a Black Widow
Every few months throughout 2023 and 2024, a package of female black widow spiders arrived at the San Diego State University chemistry department. The arachnids, jet black with a dash of red, cultivate a powerful venom that can be painful to humans. Except for that minor inconvenience, they make good subjects for studying spider silk. Their dragline silk spidroin proteins are some of the best-characterized in all spiders. And they’re available year-round, unlike some spiders that spin their webs seasonally.
Phil Degginger/Alamy; Courtesy of Gregory Holland
Six times over the course of two weeks, Johnson donned two pairs of protective gloves. Over the course of an hour, she and several students “silked” black widow spiders, which had been knocked unconscious by carbon dioxide. With tweezers, the scientists gently pulled the strand of silk from the spider’s spinnerets — the abdominal spigots that fibers emerge from — and reeled it in by winding it around a vial with a spinning motor.
“The spiders who give a ton of silk are our favorites,” Johnson said, “but I have a soft spot for the rebels who don’t want to cooperate.” Throughout the process, the researchers fed the black widows a cocktail of amino acids (like “protein shakes,” Johnson said) enriched with particular isotopes that they could detect in the lab.
Nuclear magnetic resonance (NMR) spectroscopy can map the structure of a molecule. It sends out radio frequencies to disturb the nuclei inside atoms, which then move in a way characteristic of the type of atom. Johnson used NMR on the liquid spider dope, as well as on condensates collected from the spiders’ ampullae. Meanwhile Kevin Chalek, then a postdoctoral researcher in Holland’s lab (now a researcher at the University of California, Los Angeles), mapped the atomic structure of the proteins in the solid fiber.
“We were trying to bridge the gap between what is happening when the protein is inside the spider and when it’s outside the spider,” Chalek said. “These are the same protein, [so] how can they be so different? And what exactly is happening between the two?”
Johnson observed that after she added phosphate to the liquid silk dope to start the condensation process, side groups on two amino acids (arginine and tyrosine) in the intrinsically disordered regions of the spidroin proteins started to interact weakly with one another. This interaction displaced water, organizing the disordered proteins into a denser, gel-like material — a condensate. The interaction persisted in the solid fiber, suggesting that the amino acids serve as “molecular stickers” that guide the disordered proteins into condensates and ultimately into fibers.
Dennis Kunkel Microscopy/Science Photo Library
Others on the team used AlphaFold, an artificial intelligence tool that models protein structures, and molecular dynamics software to predict this process computationally. Researchers know that spider silk’s strength comes from the sturdy beta-sheet protein structures in its final fiber. The team’s simulations showed that these amino acids line up right up at the bends in the beta sheets, suggesting that they are helping to guide the spindroins into their final structure.
“Understanding how those side groups interact and how they can develop structure that’s greater than the sum of its individual parts … is fantastic,” said Chris Holland, a biologist at the University of Sheffield who was not involved in the study and is not related to Gregory Holland. And they used real spiders, instead of synthetic silks, “which is brilliant.”
Their findings are “direct evidence” that condensates can form from native silk, which is “quite significant,” said Yang Daiwen, a biologist at the National University of Singapore who was not part of the study.
Their description of condensates doesn’t rule out earlier theories of spider silk formation. Gregory Holland, who had previously shown the presence of micelles in native spider silk, suggested that all three — micelles, condensates, and liquid crystals — could be stages of the same phase transition. Micelles that form in the liquid dope prevent the messy, disordered proteins from clumping and getting tangled. The proteins can also pre-assemble into condensates, or align into structures like liquid crystals before they are released from spinnerets as highly ordered fibers. But the actual process is likely “more dynamic and heterogenous” than sequential, Gregory Holland said, with several of these structures forming in the mixture at the same time.
Harrington agreed. “I don’t think these are mutually exclusive,” he said. “You might have different sorts of phase transitions that are occurring at different stages of the processing.”
Still, there’s more to understand about how these interactions add up on this factory line. There are likely other significant amino acid interactions that the researchers haven’t yet been able to map out in detail. They also want to look for triggers that initiate the process beyond phosphate. “There could be a range of other things that are driving structural changes in these proteins,” Chris Holland said. “We don’t know all of the switches yet.”
Superior Materials
Describing the entirety of the intricate silk-spinning process will take a lot of effort, but the payoff could be huge. Spiders produce small amounts of usable silk compared to silkworms, which have been reared for their cocoons for more than 4,000 years. It takes thousands of silkworms to make a silk shirt; it would take around 1 million spiders, in part because they don’t produce cocoons that can be easily processed. There is a more practical reason: Their cannibalistic nature makes them difficult to keep because each spider needs its own container.
Producing spider silk in the lab could result in a new range of strong yet flexible materials. Kevlar, a synthetic fiber, is currently our toughest material, but it requires processing at very high temperatures and acidic conditions. “Here, you have an organism like a spider or a mussel,” Harrington said, “which is basically making a superior material under ambient conditions in seawater or in just plain air.”
Humans haven’t figured out how to match those organisms yet. When scientists synthesize spider silk in the lab, using the exact sequence of amino acids to build a spidroin protein, the resulting silk is not as strong as natural silk. “Something is happening there that we’re also struggling to mimic,” Chalek said. He thinks additional strength must be provided by something beyond the protein’s beta sheets, arising from other aspects of silk’s structure, or perhaps from parts of the spidroin protein frequently left out of synthetic silk solutions.
“I think once we really understand those blueprints,” Chris Holland said, “we’ll be able to do more stuff with silk.”