Louis González’s research while affiliated with University of Pittsburgh and other places

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Publications (7)


Fig. 1: Conceptual illustration of how bacteria respond to a local signal. (a) Pure di↵usion: The signal di↵uses as a gradient (blue) and activates a cellular response (red). Half-Width Half-Maximum (HWHM), the distance from the maximum signal response to the point where the signal response falls to half of its maximum value, represents the extent of signal propagation. Cells show a diminishing response over time and distance. (b) Trigger wave: Incorporates both spatial coupling and feedback loops, as indicated by arrows between and within cells. Each induced cell (red) stimulates neighboring cells, thereby maintaining a constant signal propagation speed. (c) Growth-modulated di↵usion: Similar to pure di↵usion but includes the impact of cell growth dynamics on signal propagation. The signal propagates similarly to pure di↵usion and stops as cells approach the stationary phase. (d) Growth-modulated signal relay: A combination of cell growth and intercellular positive feedback. Active cell growth accelerates signal propagation before it slows down when cells enter stationary phase.
Fig. 2: (a) Circuit diagram of the sigal relay strain (IS+PF+). Erythromycin increases C4-HSL production via the RhlI synthase. C4-HSL induces the expression of sfyfp, rhlI.2TAG, and the transcription ofsupP. The rhlI.2TAG has two leucine codons replaced by amber stop codon TAG. Increased transcription of supP allows for more rhlI expression by mediating correction translation of leucin codons. (b) Schematic of experiment design illustrating cell culture in solid medium and application of exogenous signal. (c) Measured wavefront dynamics (half width half maximum HWHM) of the growth-modulated IS+PF+ strain and the dye. Shaded region corresponds to one standard deviation of triplicates. Both axes are set to a logarithmic scale.
Fig. 5: Growth modulated wavefront propagation (scaled threhold) (a) Measured wavefront dynamics (scaled threshold) for all strains. Shaded region corresponds to one standard deviation of triplicates. Both axes are set to a logarithmic scale. (bc) Measured wavefront dynamics(scaled threshold) of the IS-PF-and the IS+ PF+ strain with three di↵erent initial seeding densities. Shaded region corresponds to one standard deviation of triplicates. Both axes are set to a logarithmic scale.
Hyperballistic intercellular signaling through growth assisted positive feedback
  • Preprint
  • File available

December 2024

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20 Reads

Meidi Wang

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Louis González

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Soutick Saha

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[...]

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Matthew R Bennett

Intercellular signaling in bacteria is often mediated by small molecules secreted by cells. These small molecules disperse via diffusion which limits the speed and spatial extent of information transfer in spatially extended systems. Theory shows that a secondary signal and feedback circuits can speed up the flow of information and allow it to travel further. Here, we construct and test several synthetic circuits in Escherichia coli to determine to what extent a secondary signal and feedback can improve signal propagation in bacterial systems. We find that positive feedback-regulated secondary signals propagate further and faster than diffusion-limited signals. Additionally, the speed at which the signal propagates can accelerate in time, provided the density of the cells within the system increases. These findings provide the foundation for creating fast, long-range signal propagation circuits in spatially extended bacterial systems

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Intrinsic versus extrinsic cellular decision making

October 2024

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11 Reads

A cell routinely responds to one of many competing environmental cues. Does the cell have an intrinsic preference for that cue, or does that cue have the highest extrinsic information content? We introduce a theoretical framework to answer this fundamental question. We derive extrinsic detection limits for four types of directional cues -- external and self-generated chemical gradients, fluid flow, and contact inhibition of locomotion -- and thus predict extrinsic decision boundaries when these cues compete as pairs. Comparing the boundaries to published data from cell migration experiments quantitatively determines the degree to which cell decisions are intrinsic vs. extrinsic, revealing the extent of cells' autonomy and providing interpretation of their response networks.



Collective effects in flow-driven cell migration

November 2023

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8 Reads

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3 Citations

PHYSICAL REVIEW E

Autologous chemotaxis is the process in which cells secrete and detect molecules to determine the direction of fluid flow. Experiments and theory suggest that autologous chemotaxis fails at high cell densities because molecules from other cells interfere with a given cell's signal. We investigate autologous chemotaxis using a three-dimensional Monte Carlo-based motility simulation that couples spatial and temporal gradient sensing with cell-cell repulsion. Surprisingly, we find that when temporal gradient sensing dominates, high-density clusters chemotax faster than individual cells. To explain this observation, we propose a mechanism by which temporal gradient sensing allows cells to form a collective sensory unit. We demonstrate using computational fluid mechanics that that this mechanism indeed allows a cluster of cells to outperform single cells in terms of the detected anisotropy of the signal, a finding that we demonstrate with analytic scaling arguments. Our work suggests that collective autologous chemotaxis at high cell densities is possible and requires only known, ubiquitous cell capabilities.


Collective effects in flow-driven cell migration

May 2023

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7 Reads

Autologous chemotaxis is the process in which cells secrete and detect molecules to determine the direction of fluid flow. Experiments and theory suggest that autologous chemotaxis fails at high cell densities because molecules from other cells interfere with a given cell's signal. Based on observations of collective cell migration in diverse biological contexts, we propose a mechanism for cells to avoid this failure by forming a collective sensory unit. Formulating a simple physical model of collective autologous chemotaxis, we find that a cluster of cells can outperform single cells in terms of the detected anisotropy of the signal. We validate our results with a Monte-Carlo-based motility simulation, demonstrating that clusters chemotax faster than individual cells. Our simulation couples spatial and temporal gradient sensing with cell-cell repulsion, suggesting that our proposed mechanism requires only known, ubiquitous cell capabilities.


Autologous chemotaxis at high cell density

August 2022

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14 Reads

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6 Citations

PHYSICAL REVIEW E

Autologous chemotaxis, in which cells secrete and detect molecules to determine the direction of fluid flow, is thwarted at high cell density because molecules from other cells interfere with a given cell's signal. Using a minimal model of autologous chemotaxis, we determine the cell density at which sensing fails, and we find that it agrees with experimental observations of metastatic cancer cells. To understand this agreement, we derive a physical limit to autologous chemotaxis in terms of the cell density, the Péclet number, and the lengthscales of the cell and its environment. Surprisingly, in an environment that is uniformly oversaturated in the signaling molecule, we find that not only can sensing fail, but it can be reversed, causing backwards cell motion. Our results get to the heart of the competition between chemical and mechanical cellular sensing, and they shed light on a sensory strategy employed by cancer cells in dense tumor environments.


Autologous chemotaxis at high cell density

December 2021

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15 Reads

Autologous chemotaxis, in which cells secrete and detect molecules to determine the direction of fluid flow, is thwarted at high cell density because molecules from other cells interfere with a given cell's signal. Using a minimal model of autologous chemotaxis, we determine the cell density at which sensing fails and find that it agrees with experimental observations of metastatic cancer cells. To understand this agreement, we derive a physical limit to autologous chemotaxis in terms of the cell density, the P\'eclet number, and the length scales of the cell and its environment. Surprisingly, in an environment that is uniformly oversaturated in the signaling molecule, we find that sensing not only can fail, but can be reversed, causing backwards cell motion. Our results get to the heart of the competition between chemical and mechanical cellular sensing and shed light on a sensory strategy employed by cancer cells in dense tumor environments.

Citations (2)


... Computational research has also led to conflicting results. On one hand, Vennettilli et al. (2022) states that autologous chemotaxis fails at high density, and on the other hand, González and Mugler (2023) concludes that there exists a reversal density after which migration of a group of cells occurs collectively at a faster speed than individual migration. Most computational models of flow-induced autologous chemotaxis of multicellular systems assume that the cells are fixed (Khair 2021;Fleury et al. 2006;Fancher et al. 2020;Vennettilli et al. 2022) or that they coexist with the chemoattractant at the same spatial location (González and Mugler 2023;Waldeland and Evje 2018). ...

Reference:

Decoding complex transport patterns in flow-induced autologous chemotaxis of multicellular systems
Collective effects in flow-driven cell migration
  • Citing Article
  • November 2023

PHYSICAL REVIEW E

... Computational research has also led to conflicting results. On one hand, Vennettilli et al. (2022) states that autologous chemotaxis fails at high density, and on the other hand, González and Mugler (2023) concludes that there exists a reversal density after which migration of a group of cells occurs collectively at a faster speed than individual migration. Most computational models of flow-induced autologous chemotaxis of multicellular systems assume that the cells are fixed (Khair 2021;Fleury et al. 2006;Fancher et al. 2020;Vennettilli et al. 2022) or that they coexist with the chemoattractant at the same spatial location (González and Mugler 2023;Waldeland and Evje 2018). ...

Autologous chemotaxis at high cell density
  • Citing Article
  • August 2022

PHYSICAL REVIEW E