arXiv subjects

David S. Tourigny

Publications and source records attributed to David S. Tourigny.

9 recordsLinked to original sources

arXiv2025

Metabolic coordination and phase transitions in spatially distributed multi-cellular systems

During overflow metabolism, cells excrete glycolytic byproducts when growing under aerobic conditions in a seemingly wasteful fashion. While potentially advantageous for microbes with finite oxidative capacity, its role in higher organisms is harder to assess. Recent single-cell experiments suggest overflow metabolism arises due to imbalances in inter-cellular exchange networks. We quantitatively characterize this scenario by integrating spatial metabolic modeling with tools from statistical physics and experimental single-cell flux data. Our results provide a theoretical demonstration of how diffusion-limited exchanges shape the space of accessible multi-cellular metabolic states. Specifically, a phase transition from a balanced network of exchanges to an unbalanced, overflow regime occurs as mean glucose and oxygen uptake rates vary. Heterogeneous single-cell metabolic phenotypes occur near this transition. Time-resolved tumor-stroma co-culture data support the idea that overflow metabolism stems from failure of inter-cellular metabolic coordination. In summary, environmental control is an emergent multi-cellular property, rather than a cell-autonomous effect.

cond-mat.stat-mech↗

arXiv2023

Cell behavior in the face of uncertainty

Organisms that grow and survive in uncertain environments may need to change their physiological state as the environment changes. When the environment is uncertain, one strategy known as bet-hedging is to make these changes randomly and independently of the environment, to ensure that at least part of the population is well adapted. Organisms that collect information from their environment may also use this information to modulate their changes of physiological states. We review these different strategies and point out parallels with the theory of optimal financial investments.

q-bio.CB↗

arXiv2020

Dynamic metabolic resource allocation based on the maximum entropy principle

Organisms have evolved a variety of mechanisms to cope with the unpredictability of environmental conditions, and yet mainstream models of metabolic regulation are typically based on strict optimality principles that do not account for uncertainty. This paper introduces a dynamic metabolic modelling framework that is a synthesis of recent ideas on resource allocation and the powerful optimal control formulation of Ramkrishna and colleagues. In particular, their work is extended based on the hypothesis that cellular resources are allocated among elementary flux modes according to the principle of maximum entropy. These concepts both generalise and unify prior approaches to dynamic metabolic modelling by establishing a smooth interpolation between dynamic flux balance analysis and dynamic metabolic models without regulation. The resulting theory is successful in describing `bet-hedging' strategies employed by cell populations dealing with uncertainty in a fluctuating environment, including heterogenous resource investment, accumulation of reserves in growth-limiting conditions, and the observed behaviour of yeast growing in batch and continuous cultures. The maximum entropy principle is also shown to yield an optimal control law consistent with partitioning resources between elementary flux mode families, which has important practical implications for model reduction, selection, and simulation.

q-bio.MN↗

arXiv2020

Cooperative metabolic resource allocation in spatially-structured systems

Natural selection has shaped the evolution of cells and multi-cellular organisms such that social cooperation can often be preferred over an individualistic approach to metabolic regulation. This paper extends a framework for dynamic metabolic resource allocation based on the maximum entropy principle to spatiotemporal models of metabolism with cooperation. Much like the maximum entropy principle encapsulates `bet-hedging' behaviour displayed by organisms dealing with future uncertainty in a fluctuating environment, its cooperative extension describes how individuals adapt their metabolic resource allocation strategy to further accommodate limited knowledge about the welfare of others within a community. The resulting theory explains why local regulation of metabolic cross-feeding can fulfil a community-wide metabolic objective if individuals take into consideration an ensemble measure of total population performance as the only form of global information. The latter is likely supplied by quorum sensing in microbial systems or signalling molecules such as hormones in multi-cellular eukaryotic organisms.

q-bio.MN↗

arXiv2017

Deformed Hamiltonian vector fields and Lagrangian fibrations

Certain dissipative physical systems closely resemble Hamiltonian systems in $\mathbb{R}^{2n}$, but with the canonical equation for one of the variables in each conjugate pair rescaled by a real parameter. To generalise these dynamical systems to symplectic manifolds in this paper we introduce and study the properties of deformed Hamiltonian vector fields on Lagrangian fibrations. We describe why these objects have some interesting applications to symplectic geometry and discuss how their physical interpretation motivates new problems in mathematics.

math.SG↗

arXiv2017

Networks of planar Hamiltonian systems

We introduce diffusively coupled networks where the dynamical system at each vertex is planar Hamiltonian. The problems we address are synchronisation and an analogue of diffusion-driven Turing instability for time-dependent homogeneous states. As a consequence of the underlying Hamiltonian structure there exist unusual behaviours compared with networks of coupled limit cycle oscillators or activator-inhibitor systems.

nlin.CD↗

arXiv2014

Two-component feedback loops and deformed mechanics

It is shown that a general two-component feedback loop can be viewed as a deformed Hamiltonian system. Some of the implications of using ideas from theoretical physics to study biological processes are discussed.

q-bio.OT↗

arXiv2014

Geometric phase shifts in biological oscillators

Many intracellular processes continue to oscillate during the cell cycle. Although it is not well-understood how they are affected by discontinuities in the cellular environment, the general assumption is that oscillations remain robust provided the period of cell divisions is much larger than the period of the oscillator. Here, I will show that under these conditions a cell will in fact have to correct for an additional quantity added to the phase of oscillation upon every repetition of the cell cycle. The resulting phase shift is an analogue of the geometric phase, a curious entity first discovered in quantum mechanics. In this Letter, I will discuss the theory of the geometric phase shift and demonstrate its relevance to biological oscillations.

q-bio.MN↗

arXiv2013

Energy landscape theory for cotranslational protein folding

Energy landscape theory describes how a full-length protein can attain its native fold after sampling only a tiny fraction of all possible structures. Although protein folding is now understood to be concomitant with synthesis on the ribosome there have been few attempts to modify energy landscape theory by accounting for cotranslational folding. This paper introduces a model for cotranslational folding that leads to a natural definition of a nested energy landscape. By applying concepts drawn from submanifold differential geometry the dynamics of protein folding on the ribosome can be explored in a quantitative manner and conditions on the nested potential energy landscapes for a good cotranslational folder are obtained. A generalisation of diffusion rate theory using van Kampen's technique of composite stochastic processes is then used to account for entropic contributions and the effects of variable translation rates on cotranslational folding. This stochastic approach agrees well with experimental results and Hamiltionian formalism in the deterministic limit.

q-bio.BM↗