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Jack M. Hughes

Publications and source records attributed to Jack M. Hughes.

5 recordsLinked to original sources

How negative feedback from filamentous actin affects cell shapes and motility

The crawling motility of many eukaryotic cells is driven by filamentous actin (F-actin), and regulated by a network of signaling proteins and lipids (including small GTPases). The tangle of positive and negative feedback loops gives rise to various experimentally observed dynamic patterns (actin waves). Here we consider a recent prototypical model for actin waves in which F-actin exerts negative feedback onto a GTPase. Guided by previous numerical PDE bifurcation analysis, we explore cell shapes and motility associated with polar, oscillatory, and traveling wave solutions of a mass-conserved partial differential equation (PDE) model. We use Morpheus (cellular Potts) simulations to investigate the implications of such regimes of behavior on the shapes and motion of cells, and on transitions between modes of behavior. The model demonstrates various cell states, including resting (spatially uniform GTPase activity), polar cells (static zones of GTPase activity), and traveling waves along the cell edge. In some parameter regimes, such states can coexist, so that cells can transition from one behavior to another in response to noisy stimuli.

q-bio.CB↗

Stability of localized solutions to lattice dynamical systems

Localized patterns are spatially confined structures that arise in lattice dynamical systems and play an important role in physics, biology, and materials science. While their existence and bifurcation structure are well-understood, the stability of these solutions remains largely unexplored, particularly in discrete and high-dimensional settings. In this work, we develop a general theoretical framework to analyze the spectral stability of localized steady states in one-dimensional and multi-dimensional rectangular lattices. Our approach leverages the properties of front and back solutions, combined with a discrete Evans function formulation, to characterize the spectrum of localized solutions. We prove that, for well-separated regions of localization, the Evans function asymptotically factorizes into contributions from the underlying fronts and backs, allowing explicit counting of unstable eigenvalues. This framework applies to solutions with single or multiple plateaus, including oscillatory and multi-pulse configurations. We illustrate the results on a real-valued cubic-quintic Ginzburg-Landau lattice, a prototypical Nagumo-type system, and provide numerical demonstrations of bifurcation structures and eigenvalue spectra.

nlin.PS↗

Bistability of travelling waves and wave-pinning states in a mass-conserved reaction-diffusion system: From bifurcations to implications for actin waves

Eukaryotic cells demonstrate a wide variety of dynamic patterns of filamentous actin (F-actin) and its regulators. Some of these patterns play important roles in cell functions, such as distinct motility modes, which motivate this study. We devise a mass-conserved reaction-diffusion model for active and inactive Rho-GTPase and F-actin in the cell cortex. The mass-conserved Rho-GTPase system promotes F-actin, which feeds back to inactivate the former. We study the model on a 1D periodic domain (edge of thin sheet-like cell) using bifurcation theory in the framework of spatial dynamics, complemented with numerical simulations. Among several discussed bifurcations, the analysis centers on the study of the codimension-2 long wavelength and finite wavenumber Hopf instability, in which we describe a rich structure of steady wave-pinning states (a.k.a. mesas, obeying the Maxwell construction), propagating coherent solutions (fronts and excitable pulses), and travelling and standing waves, all distinguished by mass conservation regimes and classified by domain sizes. Specifically, we highlight the unexpected conditions for bistability between steady wave-pinning and travelling wave states on moderate domain sizes, i.e., unfolding through domain length. These results uncover and exemplify possible mechanisms of coexistence, robustness, and transitions between distinct cellular motility modes, including directed migration, turning, and ruffling. More broadly, the results indicate that non-gradient reaction-diffusion models comprising mass conservation have distinct pattern formation mechanisms that motivate further investigations, such as the unfolding of codimension-3 instabilities and T-points.

nlin.PS↗

A mass conserved reaction-diffusion system reveals switching between coexisting polar and oscillatory cell motility states

Motile eukaryotic cells display distinct modes of migration that often occur within the same cell type. It remains unclear, however, whether transitions between the migratory modes require changes in external conditions, or whether the different modes are coexisting states that emerge from the underlying signaling network. Using a simplified mass-conserved reaction-diffusion model of small GTPase signaling with F-actin mediated feedback, we uncover a distinct bistable mechanism (involving gradient-like phase-separation and traveling waves) and a regime where a polarized mode of migration coexists with spatiotemporal oscillations; the latter, in larger domains, including in three-dimensional surface geometry, result in disordered patterns even in the absence of noise or shape deformations. Indeed, experimental observations of D. discoideum show that, upon collision with a rigid boundary, cells may switch from polarized to disordered motion.

nlin.PS↗

Travelling waves in a PDE-ODE coupled system with nonlinear diffusion

We analyze travelling wave (TW) solutions for nonlinear systems consisting of an ODE coupled to a degenerate PDE with a diffusion coefficient that vanishes as the solution tends to zero and blows up as it approaches its maximum value. Stable TW solutions for such systems have previously been observed numerically as well as in biological experiments on the growth of cellulolytic biofilms. In this work, we provide an analytical justification for these observations and prove existence and stability results for TW solutions of such models. Using the TW ansatz and a first integral, the system is reduced to an autonomous dynamical system with two unknowns. Analysing the system in the corresponding phase-plane, the existence of a unique TW is shown, which possesses a sharp front and a diffusive tail, and is moving with a constant speed. The linear stability of the TW in two space dimensions is proven under suitable assumptions on the initial data. Finally, numerical simulations are presented that affirm the theoretical predictions on the existence, stability, and parametric dependence of the TWs.

math.AP↗