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Jupiter Algorta @jupiteralgorta.bsky.social · May 6

If you're curious about how cells make decisions in complex environments, and how mathematical models can capture such behaviour, our preprint is now live!
Check it out here: www.biorxiv.org/content/10.1...

Investigating Local Negative Feedback of Rac Activity by Mathematical Models and Cell Motility Simulations

For polarization and directed migration, cells use a combination of local positive feedback and long-range inhibition. We have previously used mathematical models to show the ability of this core…

www.biorxiv.org

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Jupiter Algorta @jupiteralgorta.bsky.social · May 6

Following a hypothesis proposed by Orion and Jason, I tested multiple models and formalisms to explain how cell reversal could be explained.
The key was adding a negative feedback loop (a Rac inhibitor) to the molecules driving cell motion.
With this, simulations finally matched experiments.

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Jupiter Algorta @jupiteralgorta.bsky.social · May 6

But when the light expands from part of the cell to illuminate the whole cell, real cells reverse rotation, something previous model(s) failed to predict.
This and other puzzling results led us to revise such models to better understand how cells reorient.

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Jupiter Algorta @jupiteralgorta.bsky.social · May 6

When the light hits one side of the cell, it smoothly reorients toward it.
In simple environments, a previous polarity model captured this motion well.

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Jupiter Algorta @jupiteralgorta.bsky.social · May 6

In 2023, Dr. Orion Weiner and Dr. Jason Town (UCSF) showed how to guide cells with light, using “optogenetic” stimulation upstream of Rac t o steer neutrophils .
Before diving deeper, here’s what you’ll see:
Left = experiment, right = simulation.
Green = cell edge, blue = light stimulus.

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Jupiter Algorta @jupiteralgorta.bsky.social · May 6

Previous models of cell polarity capture basic movements, but not flexibility. When the chemical signal changes direction, they stay locked in place. Our revised model (right) reorients and tracks the new direction. We’re releasing the full story today as a preprint – link below.

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Jupiter Algorta @jupiteralgorta.bsky.social · May 6

A cell navigating a chemical gradient is like being blindfolded in a dense forest, trying to find a clearing by feeling slight changes in the breeze. No map, no clear path. And yet, immune cells can find their way. I build models to understand how.

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Jupiter Algorta @jupiteralgorta.bsky.social · May 6

Check this fascinating footage: a neutrophil navigating towards a micropipette. These cells can not only navigate complex, noisy environments, but also rapidly reorient to new cues. Curious about how they do it? Keep reading!

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Jupiter Algorta @jupiteralgorta.bsky.social · May 6

In 2023, Dr. Orion Weiner and Dr. Jason Town (UCSF) showed how to guide cells with light, using “optogenetic” stimulation upstream of Rac t o steer neutrophils .
Before diving deeper, here’s what you’ll see:
Left = experiment, right = simulation.
Green = cell edge, blue = light stimulus.

Jupiter Algorta @jupiteralgorta.bsky.social · May 6

Previous models of cell polarity capture basic movements, but not flexibility. When the chemical signal changes direction, they stay locked in place. Our revised model (right) reorients and tracks the new direction. We’re releasing the full story today as a preprint – link below.

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Jupiter Algorta @jupiteralgorta.bsky.social · May 6

A cell navigating a chemical gradient is like being blindfolded in a dense forest, trying to find a clearing by feeling slight changes in the breeze. No map, no clear path. And yet, immune cells can find their way. I build models to understand how.

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

If any of this interests you, I invite you to visit Morpheus's home page: morpheus.gitlab.io and feel free to contact me at [email protected].

Morpheus

Multicellular Simulation

morpheus.gitlab.io

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

Here’s a short video of one of my simulated cells responding to optogenetic inputs: the green shows Rac concentration on the cell edge, and the blue dashed circles indicate the regions of optogenetic stimulation, mimicking their experimental setup.

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

This project involves crafting intricate PDEs and implementing them in Morpheus to test and elaborate on what they’ve observed in the lab.

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

My role has been to model their cells and demonstrate how incorporating this hypothesis enhances the ability of virtual cells to realign their fronts during chemotaxis. Additionally, I’ve been working to explain Jason’s most surprising results.

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

In 2023, Jason published a paper presenting compelling evidence for a local inhibitor of Rac within its downstream effects, along with extensive data and some unexpected results from different light stimulation configurations.

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

Most recently, I have been collaborating with Dr. Orion Weiner and Dr. Jason Town to model HL-60 neutrophil-like cells modified to respond to optogenetic stimulation.

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

Soon you’ll be able to read about it in a review paper I co-authored with Dr. Leah Keshet, Jack M. Hughes, and Ali Fele-Paranj. The paper has been accepted and will be featured in the next Cold Spring Harbor Perspectives volume on Cell Migration. Here’s a video of the project in action:

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

This project was particularly refined as it incorporated two stages of cellular differentiation, governed by internal gene expressions, and cell sorting driven by differential cell-cell adhesion forces.

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

Another interesting project I developed in Morpheus over the years was a simulation of mammalian embryo development, starting from a single zygote cell and progressing to the 128-cell stage.

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

I highly recommend trying out this tool and following along with the tutorial. By the end, you should be able to craft simulations like this one where I have two cells that follow a chemical gradient through chemotaxis:

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

I demonstrate this in the video tutorials I created a few years ago, which you can find here (though I still need to complete Part 3, it provides a great starting point): www.youtube.com/watch?v=DLNj.... Yes, I know… I had my head shaved at the time, and it looks a bit weird!

Morpheus Tutorial - Part 1 Description, Space, and Time

YouTube video by Jupiter Algorta

www.youtube.com

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

The software features a user-friendly graphical interface, where users can simply drag and drop elements to build and customize their virtual cellular environments.

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

In 2014, a group at TU Dresden—Jörn Starruß, Walter de Back, Lutz Brusch, and Andreas Deutsch—created Morpheus, a software designed to allow users to implement their models with little to no programming knowledge.

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Jupiter Algorta @jupiteralgorta.bsky.social · Jan 20

Over the years, CPM has evolved to include increasingly complex descriptions and fascinating dynamics, making it an indispensable tool for exploring cellular behaviour. With its growing popularity, many software tools and packages were developed to facilitate the implementation of CPM.

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