Conducting a Cell Orchestra

A conceptual bioelectricity review

Source.
The inverse problem.

How do systems detect when their shape has been altered by injury or disease, compute what steps to take to restore their correct form, and decide when to stop growing (after their anatomical goal has been reached)?

Salamander tail remodelling. Source.
How membrane potential affects cell cycle progression. Source.
Cancer cells (highly dividing) in a tumour are more depolarized than the cells around it. Source.
Source.

Attractor States

An attractor state. Source.
if damaged (current pattern doesn’t resemble encoded target pattern):
issue commands to individual cells to bring overall pattern one step closer to the target morphology
if current pattern = target pattern:
stop
else:
repeat
An attractor state ver. frog. Source.
  • Gene editing: trying to change the shape of an anthill by changing each individual ant’s behaviour.
    Modifying bioelectricity: having the power of Dr. Dolittle and being able to speak to ants to build a different anthill.
  • Gene editing: regulating the velocity of each molecule in a gas
    Modifying bioelectricity: changing the temperature and pressure
  • Gene editing: changing your phone wallpaper by taking out the motherboard and changing each transistor.
    Modifying bioelectricity: tapping some buttons on your screen.

DNA provides the instructions, bioelectricity decides which instructions to follow.

Pattern Formation

Pre-pattern of a frog’s face. Source.

Multistability

Planaria doing their regenerating thing. Source.
Source.
Source.
Tetrastability but the main idea is the same as bistability. Source
Source.
Above: computer-designed xenobot design. Below: real-life xenobot constructed from xenopus laevis stem cells.

Feedback Loops

(A) An example of a bioelectrical feedback loop. Source.

Methods

Source.

Problems cracking the morphogenetic code can solve

Source.
Left: bioreactor containing progesterone. Right: leg regeneration process. Video.
Reparing frog brain development with bioelectric drugs. Source.
An functional eye growing on a tadpole’s butt. Video.

The future

  • Diagnoses. Remember the image near the beginning of this article where you could physically see the different resting membrane potential of a tumour vs the area around it? Bioelectricity could provide a non-invasive and precise way of diagnosing illnesses.
  • Microdomains. For the entirety of this article, we’ve been referring to bioelectricity as the average of all charges in an area. But, different areas of a cell membrane have different charges. The organelles inside of cells also have multiple charges. Exploring these microdomains could provide us with an even more high-quality understanding of how cells work.
  • I’ll let Michael Levin explain the last point:

How you can also be a cell-whisperer

TL;DR

  • Bioelectricity is the movement of ions across a cell membrane — changing the resting membrane potential (Vmem)
  • A hyperpolarized Vmem transitions cells from G1 to S in the cell cycle and its DNA is replicated. A depolarized Vmem transitions cells from G2 to M in the cell cycle, and mitosis occurs (increased cell growth).
  • Anatomy is not hardcoded in the DNA. Cells have an attractor state (ex. anatomical homeostasis) that represents what they’re supposed to look like. They then compute the necessary actions to reach the attractor state.
  • Cells can have multiple attractors states and their states can also be changed (ex. double-headed planaria & xenobots).
  • DNA is the hardware of the cell, bioelectricity is the software. To change cell behaviour, we don’t necessarily need to edit the DNA, we can simply input some ions, change their attractor state, and the cell will figure out how to reach that state by themselves. It’s similar to calling predetermined functions like buildAnEye() instead of coding everything with 1s and 0s.
  • Pattern formation is when cells take on different identities and assemble themselves in the correct place and orientation (to form tissues and organs). Morphogens facilitate pattern formation.
  • Cells determine when to stop growing with positive and negative feedback loops.
  • Bioelectricity can be changed with ion channel inhibiting/activating drugs or through gene editing ion channels.
  • Problems that bioelectricity can help solve: cancer, regeneration, birth defects, ageing.

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