Michael Levin Bioelectricity 101 Crash Course Lesson 30: Morphospace: Discovering the Potential of Cellular Self-Organization Summary

• Morphospace is a conceptual “space” representing all possible biological forms or structures that could exist, given the basic building blocks of life (cells, tissues, etc.). It’s not a physical space, but a space of possibilities.
• The morphospace that an organism explores in standard development is the space for all possible forms given typical, evolved development of that organism. It would be narrow – typical development gives typical anatomy.
• Cells have the latent potential to create a much wider range of structures than they normally do during typical development or regeneration.
• Experiments that disrupt normal bioelectric signaling (or other developmental cues) can “push” cells into new regions of morphospace, revealing this hidden potential.
• Xenobots are a prime example: frog skin cells, freed from their usual context, self-organize into novel, motile forms that don’t exist in nature, demonstrating exploration of morphospace.
• Morphospace isn’t just about shape; it can also include behaviors, physiological functions, and even cognitive capabilities.
• Understanding morphospace has implications for regenerative medicine (exploring novel repair strategies), synthetic biology (designing new biological forms), and understanding the limits and possibilities of life itself.
• The exploration of morphospace implies some kind of pre-existing ‘possibility space’ which is selected upon. This does not require a design – just the capacity of tissues, responding to changes, with natural selection favouring novel adaption of that existing ability.

Michael Levin Bioelectricity 101 Crash Course Lesson 30: Morphospace: Discovering the Potential of Cellular Self-Organization

So far in this course, we’ve seen how bioelectricity plays a crucial role in guiding development, regeneration, and maintaining the correct form of an organism. We’ve learned that cells are not simply following a rigid genetic program, but are constantly communicating and coordinating their actions, like a collective intelligence. They possess a kind of “shape memory” that helps them rebuild damaged tissues and, in some remarkable cases like the planarian, even regenerate entire bodies.

But what are the limits of this cellular capability? Are cells strictly limited to building the structures we see in nature, or do they have the potential to create something… more? This is where the concept of morphospace comes in. It’s a powerful idea that helps us understand the hidden potential of living systems.

The word “morphospace” combines “morpho-” (meaning form or shape) and “space.” But it’s important to understand that morphospace is not a physical space, like the space you occupy in a room. It’s a conceptual space – a space of possibilities. Think of it as a vast, multi-dimensional landscape representing all possible biological forms that could exist, given the fundamental building blocks of life (cells, tissues, their interactions, etc.).

Imagine a giant library filled with every book that could ever be written using the letters of the alphabet. Most of these books would be gibberish, but some would be meaningful sentences, paragraphs, stories, or even entire novels. Morphospace is like that library, but instead of letters, the basic elements are cells, and instead of books, the possibilities are biological structures – organs, limbs, entire organisms, and even things that don’t exist in nature.

Now, under normal circumstances, an organism like a frog or a human only explores a very small region of this vast morphospace. During development, a fertilized egg follows a well-defined pathway, guided by genetic and bioelectric signals, to produce the typical body plan of its species. This pathway is like a well-trodden path through the morphospace landscape. It’s a reliable, predictable route that leads to a functional, viable organism. This is also similar during the standard regeneration that planaria exhibit. The “normal” regeneration to one-head, one-tail is like taking the well-trodden pathway, like during standard development.

But what happens if we disrupt that normal pathway? What if we “push” the cells off the beaten path and into unexplored territory? This is precisely what Michael Levin and his colleagues have done in a series of remarkable experiments.

The most striking example is the creation of Xenobots. As we discussed in an earlier lesson, Xenobots are tiny, living structures assembled from frog skin cells. Normally, these skin cells would just sit on the surface of a tadpole, protecting it from the environment. But when these cells are isolated and placed in a new context, something astonishing happens: they self-organize into completely novel forms.

These Xenobots are not “designed” in the traditional sense. There’s no blueprint or detailed set of instructions telling them how to assemble. Instead, the cells use their inherent abilities – their ability to stick together, to move, to communicate with each other via bioelectric and mechanical signals – to explore a new region of morphospace. They find a new stable state, a new form that is viable and, in some cases, even capable of simple behaviors like movement and collective action.

This is a profound demonstration of the latent potential of cells. They’re not just passive building blocks; they’re active agents that can explore morphospace and find new solutions to the problem of “being a living thing.” The standard development of an embryo is a narrow range of the available possibilities that cells are capable of producing. They’re capable of self-organization to a much wider set of forms.

Think of it like clay. You can mold clay into a specific shape, like a cup or a plate. These are the “normal” forms you might expect. But clay also has the potential to be molded into countless other shapes – sculptures, abstract forms, things you’ve never seen before. The specific form the clay takes depends on how you manipulate it, what forces you apply.

Similarly, cells have the potential to create a much wider range of structures than they normally do. This potential is revealed when we alter their environment, disrupt their normal communication patterns, or change the bioelectric “landscape” in which they exist. Disrupting the normal pathways shows this – such as blocking gap junctions to make the 2-headed planaria.

It’s important to note that morphospace isn’t just about shape. It also encompasses behavior, physiological function, and even cognitive capabilities. Xenobots, for example, not only have a novel shape, but they also exhibit novel behaviors, like moving in circles, aggregating particles, and even showing a rudimentary form of collective decision-making. These behaviors are not explicitly programmed into them; they emerge from the interactions of the cells within their new form.

So, morphospace is a multi-dimensional space that includes not just physical structure, but also function and behavior. Exploring this space helps us understand the fundamental principles of biological organization, the limits of what’s possible, and the potential for creating new forms of life.

What are the implications of understanding morphospace?

• Regenerative Medicine: By understanding how cells explore morphospace, we might be able to develop new strategies for repairing damaged tissues and organs. Instead of trying to force cells to regrow a specific structure (like a limb), we might be able to “nudge” them into a new region of morphospace where they find their own way to achieve a functional outcome.
• Synthetic Biology: Morphospace provides a framework for designing entirely new biological forms and functions. We can use our understanding of bioelectric signaling and cellular self-organization to create “living machines” with specific capabilities.
• Understanding Life: Exploring morphospace helps us answer fundamental questions about life itself. What are the limits of biological form and function? How did evolution discover the particular forms we see in nature? What other forms could have evolved, but didn’t?

In a sense, morphospace is a reminder of the incredible plasticity and creativity of living systems. Cells are not simply following a rigid set of instructions; they’re constantly exploring, adapting, and finding new ways to organize themselves. By understanding and manipulating this process, we can unlock a whole new world of possibilities in medicine, biotechnology, and our fundamental understanding of life.

Michael Levin Bioelectricity 101 Crash Course Lesson 30: Morphospace: Discovering the Potential of Cellular Self-Organization Quiz

1. Morphospace is best defined as:

A) The physical space occupied by an organism.
B) A conceptual space representing all possible biological forms.
C) The set of genes that control development.
D) The process of cell division.

2. During normal development, an organism typically explores:

A) The entire morphospace.
B) A very small region of morphospace.
C) A random selection of points in morphospace.
D) Only the parts of morphospace related to its behavior.

3. Xenobots are an example of:

A) Cells following a pre-programmed genetic blueprint.
B) Cells exploring a novel region of morphospace.
C) Cells reverting to their original function as skin cells.
D) Cells losing their ability to self-organize.

4. The latent potential of cells refers to:

A) Their ability to create only the structures seen in nature.
B) Their ability to create a much wider range of structures than they normally do.
C) Their inability to adapt to new environments.
D) Their strict adherence to a genetic program.

5. Which of the following can “push” cells into new regions of morphospace?

A) Maintaining normal developmental conditions.
B) Disrupting normal bioelectric signaling.
C) Providing cells with a detailed blueprint for a new structure.
D) Preventing cells from communicating with each other.

6. Morphospace includes not only physical shape but also:

A) Only behavior.
B) Only physiological function.
C) Behavior, physiological function, and even cognitive capabilities.
D) Only the genetic code.

7. Understanding morphospace has implications for:

A) Regenerative medicine.
B) Synthetic biology.
C) Understanding the limits and possibilities of life.
D) All of the above.

8. Clay is used as an analogy to illustrate:

A) The rigid structure of DNA.
B) The latent potential of cells to create diverse forms.
C) The rapid firing of action potentials.
D) The process of chemical signaling.

9. The standard model for development and regeneration assumes:

A) The discovery of all capabilities for tissues are already known.
B) Cells cannot regenerate.
C) Only the genes give an absolute structure that tissues and cells can be.
D) Cells follow predictable pathways during normal circumstances.

10. True or False: Morphospace is a physical space that cells can move through.

A) True
B) False

11. True of False: Cells are merely building blocks.

A) True
B) False

12. Xenobots are made from:

A) Human skin cells.
B) Frog skin cells.
C) Plant cells.
D) Bacterial cells.

13. Xenobots new behavior…

A) Is an accidental occurance.
B) Demonstrates cellular potential
C) Shows new behaviors in a new bioelectric/structural arrangement.
D) All of the Above.

14. In the analogy of a library of all possible books, what do the letters of the alphabet represent?

A) Genes
B) Cells
C) Organs
D) Organisms

15. By disrupting _______, scientists revealed that cells have a greater range of forms than they usually do.

A) Normal developmental pathways
B) Gravitational forces
C) Standard, evolved development and regeneration
D) A and C.

16. Which is the following capabilities demonstrates best “revealing an unexpected discovery of morphospace?”

A) tadpoles growing to a frog
B) the planaria regenerating to 1-head, 1 tail.
C) human stem cells creating small versions of human organs.
D) Xenobots moving around in novel, collective ways.

17. If a cell *always* did what it was predicted to do during development or regeneration, its explorable area of morphospace is said to be:

A) Tiny.
B) Wide.
C) Robust
D) Infinite

18. The ability for cells to build *more* structures highlights the _______ potential of them:

A) Fixed
B) Small
C) Latent
D) Pre-Programmed.

19. Levin’s experiements seek to better explore morphospace and therefore implies:

A) Cells are fundamentally able to organize to many solutions.
B) Evolution picked the *best* or *only* set of solutions.
C) Any configuration is theoretically available to a cell.
D) Only a very small range is, and what we usually see during life is all.

20. Exploring morphospace involves finding how _____ biological organizations can possibly exist:

A) Many
B) Robust
C) Different.
D) All of the above.

Michael Levin Bioelectricity 101 Crash Course Lesson 30: Morphospace: Discovering the Potential of Cellular Self-Organization Answer Sheet

1. B

2. B

3. B

4. B

5. B

6. C

7. D

8. B

9. D

10. B

11. B

12. B

13. D

14. B

15. D

16. D

17. A

18. C

19. A

20. D

迈克尔·莱文 生物电 101 速成课程 第30课：形态空间：发现细胞自组织的潜力 摘要

• 形态空间是一个概念性的“空间”，代表了在给定生命基本构建块（细胞、组织等）的情况下，可能存在的所有生物形式或结构。它不是一个物理空间，而是一个可能性空间。
• 生物体在标准发育过程中探索的形态空间，是在该生物体典型、进化发育情况下所有可能形式的空间。 这个空间会很窄——典型的发育产生典型的解剖结构。
• 细胞具有潜在的能力，可以创造出比它们在典型发育或再生过程中通常产生的结构范围更广的结构。
• 干扰正常生物电信号（或其他发育线索）的实验可以将细胞“推”入形态空间的新区域，揭示这种隐藏的潜力。
• 异种机器人(Xenobots)就是一个很好的例子：从正常环境中解放出来的青蛙皮肤细胞，自组织成自然界中不存在的新型运动形式，证明了对形态空间的探索。
• 形态空间不仅仅关乎形状；它还可以包括行为、生理功能，甚至认知能力。
• 理解形态空间对再生医学（探索新的修复策略）、合成生物学（设计新的生物形式）以及理解生命的极限和可能性具有重要意义。
• 形态空间的探索暗示了某种预先存在的“可能性空间”，它是被选择的。 这不需要设计——只需要组织响应变化的能力，自然选择有利于对现有能力的新的适应。

迈克尔·莱文 生物电 101 速成课程 第30课：形态空间：发现细胞自组织的潜力

到目前为止，在本课程中，我们已经看到生物电如何在引导发育、再生和维持生物体的正确形态方面发挥着至关重要的作用。 我们已经了解到，细胞不仅仅是遵循僵化的基因程序，而是像集体智慧一样不断地交流和协调它们的行为。 它们拥有一种“形态记忆”，可以帮助它们重建受损的组织，并且在某些显著的例子中，如涡虫，甚至可以再生整个身体。

但是这种细胞能力的极限是什么？ 细胞是否严格限于构建我们在自然界中看到的结构，或者它们是否有潜力创造出……更多的东西？ 这就是形态空间概念的用武之地。 这是一个强有力的概念，可以帮助我们理解生命系统的隐藏潜力。

“形态空间”一词结合了“morpho-”（意为形式或形状）和“空间”。 但重要的是要理解，形态空间不是物理空间，就像你在房间里占据的空间一样。 它是一个概念性空间——一个可能性空间。 可以把它想象成一个巨大的、多维的景观，代表了在给定生命的基本构建块（细胞、组织、它们的相互作用等）的情况下可能存在的所有生物形式。

想象一个巨大的图书馆，里面装满了所有可能用字母表中的字母写成的书。 这些书大多数都是胡言乱语，但有些会是有意义的句子、段落、故事，甚至是整部小说。 形态空间就像那个图书馆，但基本元素不是字母，而是细胞，可能性也不是书籍，而是生物结构——器官、四肢、整个生物体，甚至是自然界中不存在的东西。

现在，在正常情况下，像青蛙或人类这样的生物体只探索这个巨大形态空间中一个非常小的区域。 在发育过程中，受精卵遵循明确的路径，在基因和生物电信号的引导下，产生其物种的典型身体结构。 这条路径就像一条穿过形态空间景观的、被充分践踏的道路。 这是一条可靠、可预测的路线，可以产生一个功能性、可存活的生物体。 这也类似于涡虫表现出的标准再生。 “正常”再生为一头一尾就像走那条老路，就像标准发育一样。

但是，如果我们扰乱了这条正常的路径会怎么样呢？ 如果我们将细胞“推”离老路并进入未探索的领域呢？ 这正是迈克尔·莱文和他的同事们在一系列非凡的实验中所做的。

最引人注目的例子是异种机器人 (Xenobots) 的创造。 正如我们在前面的课程中讨论的那样，异种机器人是由青蛙皮肤细胞组装而成的微小、活体结构。 通常，这些皮肤细胞只会位于蝌蚪的表面，保护它免受环境影响。 但是当这些细胞被分离并放置在一个新的环境中时，令人惊讶的事情发生了：它们自组织成全新的形式。

这些异种机器人不是传统意义上的“设计”。 没有蓝图或详细的指令告诉它们如何组装。 相反，细胞利用它们的内在能力——它们粘在一起、移动、通过生物电和机械信号相互交流的能力——来探索形态空间的一个新区域。 他们找到了一种新的稳定状态，一种可存活的新形式，在某些情况下，甚至能够进行简单的行为，如运动和集体行动。

这是细胞潜在能力的一个深刻证明。 它们不仅仅是被动的构建块； 它们是积极的主体，可以探索形态空间并找到“成为生命体”这一问题的新解决方案。 胚胎的标准发育是细胞能够产生的可用可能性的一个狭窄范围。 它们能够自组织成更广泛的形式。

可以把它想象成粘土。 你可以将粘土塑造成特定的形状，如杯子或盘子。 这些是你可能期望的“正常”形式。 但粘土也有潜力被塑造成无数其他形状——雕塑、抽象形式，你从未见过的东西。 粘土采取的具体形式取决于你如何操纵它，你施加了什么力。

同样，细胞有潜力创造出比它们通常产生的范围更广的结构。 当我们改变它们的环境、扰乱它们正常的交流模式或改变它们存在的生物电“景观”时，这种潜力就会显现出来。 扰乱正常路径表明了这一点 – 例如阻断间隙连接以制造双头涡虫。

重要的是要注意，形态空间不仅仅关乎形状。 它还包括行为、生理功能，甚至认知能力。 例如，异种机器人不仅具有新颖的形状，而且还表现出新颖的行为，如绕圈运动、聚集颗粒，甚至表现出一种基本的集体决策形式。 这些行为并没有明确地编入它们体内； 它们是从细胞在其新形式内的相互作用中涌现出来的。

因此，形态空间是一个多维空间，不仅包括物理结构，还包括功能和行为。 探索这个空间有助于我们理解生物组织的基本原理、可能性的极限以及创造新生命形式的潜力。

理解形态空间有什么意义？

• 再生医学： 通过了解细胞如何探索形态空间，我们也许能够开发出修复受损组织和器官的新策略。 与其试图强迫细胞再生特定结构（如肢体），我们也许能够将它们“推”入形态空间的一个新区域，在那里它们可以找到自己的方法来实现功能性结果。
• 合成生物学： 形态空间为设计全新的生物形式和功能提供了一个框架。 我们可以利用我们对生物电信号和细胞自组织的理解来创造具有特定能力的“活机器”。
• 理解生命： 探索形态空间有助于我们回答关于生命本身的基本问题。 生物形式和功能的极限是什么？ 进化是如何发现我们在自然界中看到的特定形式的？ 还有哪些形式可能已经进化，但没有进化？

在某种意义上，形态空间提醒我们生命系统具有令人难以置信的可塑性和创造力。 细胞不仅仅是遵循一套僵化的指令； 它们不断地探索、适应，并找到组织自己的新方法。 通过理解和操纵这个过程，我们可以在医学、生物技术和我们对生命的基本理解方面开启一个全新的可能性世界。

迈克尔·莱文 生物电 101 速成课程 第30课：形态空间：发现细胞自组织的潜力 小测验

1. 形态空间最好定义为：

A) 生物体占据的物理空间。
B) 代表所有可能生物形式的概念空间。
C) 控制发育的基因组。
D) 细胞分裂的过程。

2. 在正常发育过程中，生物体通常会探索：

A) 整个形态空间。
B) 形态空间的一个非常小的区域。
C) 形态空间中点的随机选择。
D) 仅与行为相关的形态空间部分。

3. 异种机器人是以下哪一项的一个例子：

A) 细胞遵循预先编程的基因蓝图。
B) 细胞探索形态空间的一个新区域。
C) 细胞恢复其作为皮肤细胞的原始功能。
D) 细胞失去自组织能力。

4. 细胞的潜在能力是指：

A) 它们仅创造自然界中可见结构的能力。
B) 它们创造比通常产生的结构范围更广的结构的能力。
C) 它们无法适应新环境。
D) 它们严格遵守基因程序。

5. 以下哪一项可以将细胞“推”入形态空间的新区域？

A) 维持正常的发育条件。
B) 扰乱正常的生物电信号。
C) 为细胞提供新结构的详细蓝图。
D) 阻止细胞相互交流。

6. 形态空间不仅包括物理形状，还包括：

A) 仅行为。
B) 仅生理功能。
C) 行为、生理功能，甚至认知能力。
D) 仅基因代码。

7. 理解形态空间具有以下意义：

A) 再生医学。
B) 合成生物学。
C) 理解生命的极限和可能性。
D) 以上都是。

8. 粘土被用作类比来说明：

A) DNA 的刚性结构。
B) 细胞创造不同形式的潜在能力。
C) 动作电位的快速放电。
D) 化学信号传导过程。

9. 发育和再生的标准模型假设：

A) 已经发现了组织所有能力的发现。
B) 细胞不能再生。
C) 只有基因才能提供组织和细胞的绝对结构。
D) 细胞在正常情况下遵循可预测的途径。

10. 对或错：形态空间是细胞可以移动的物理空间。

A) 对
B) 错

11. 对或错：细胞仅仅是构建块。

A) 对
B) 错

12. 异种机器人由以下哪种细胞制成：

A) 人类皮肤细胞。
B) 青蛙皮肤细胞。
C) 植物细胞。
D) 细菌细胞。

13. 异种机器人的新行为……

A) 是一种偶然事件。
B) 表明细胞的潜力
C) 在新的生物电/结构排列中显示出新的行为。
D) 以上都是。

14. 在所有可能书籍的图书馆的类比中，字母表的字母代表什么？

A) 基因
B) 细胞
C) 器官
D) 生物体

15. 通过扰乱 _______，科学家们发现细胞具有比通常产生的形式范围更广的形式。

A) 正常发育途径
B) 引力
C) 标准的、进化的发育和再生
D) A 和 C。

16. 以下哪种能力最能证明“揭示了形态空间的意外发现”？

A) 蝌蚪长成青蛙
B) 涡虫再生为一头一尾。
C) 人类干细胞产生人类器官的小型版本。
D) 异种机器人以新颖的集体方式移动。

17. 如果一个细胞总是按照其在发育或再生过程中的预测行事，那么它的形态空间的可探索区域就被认为是：

A) 微小的。
B) 宽阔的。
C) 强大的
D) 无限的

18. 细胞构建更多结构的能力突出了它们的 _______ 潜力：

A) 固定的
B) 小的
C) 潜在的
D) 预编程的。

19. 莱文的实验试图更好地探索形态空间，因此暗示：

A) 细胞基本上能够组织成许多解决方案。
B) 进化选择了最好或唯一的一组解决方案。
C) 理论上任何配置都可用于细胞。
D) 只有一个非常小的范围，我们在生活中通常看到的就是全部。

20. 探索形态空间涉及找到 _____ 生物组织可能存在：

A) 许多
B) 强大的
C) 不同的。
D) 以上都是。

迈克尔·莱文 生物电 101 速成课程 第30课：形态空间：发现细胞自组织的潜力 答案表

1. B

2. B

3. B

4. B

5. B

6. C

7. D

8. B

9. D

10. B

11. B

12. B

13. D

14. B

15. D

16. D

17. A

18. C

19. A

20. D